As you play though the levels, you must defeat and trap Boos. There are 5 phases to traping a Ghost.
- Detection: Use your Boo Radar and Spook Goggles to find the Ghost.
- Dispersion: Use your weaponary to disperse the Ghost's energy (Each type of Ghost is weak to a difrent weapon). Corporeal beings (Non-Ghost enemies) are destoyed after this phrase.
- Detention: Use your capture stream to hold the Ghost in place.
- Daze and Destroy: With the Ghost in your grasp, slam the Ghost about until it is stunned.
- FINISH HIM!: Suck the disabled Ghost into your Poltergust.
Along the way, you will gain new weapons for your Poltergust to deal with difrent Ghosts.
- The Particle Beam is your basic weapon for the dispersion of paranormal energy. It is the first weapon you get.
- The Slime Thrower Mk. II uses psoitvly charged ectoplasam to attack foes. It is capable of exorcising possesed Toads and destroying evil Black Slime and creatures created by it.
- The Dark Matter Cannon acts as an anti-specter shotgun, capable of damaging large groups of foes in close quarters. It is powerful at close range, but becomes weaker the farther you are from your target.
- The Meson Blaster fires bulletlike projectiles that home in on enemies. It is best used on bosses with visable weaknesses.
Between each level, you visit the firehouse to advance in the story. Once you meet the nesisary requirements, you can board Spectro-1 to progress to the next level. At the end of the level, you must face a Boss Ghost to progress through the level
The game opens at the Mushroom City Natural History Museum, two years after the events of the second movie. One of the museum's night guards is watching TV (where an ad for the Boobusters is running) rather than paying attention to the security monitors. His attention is suddenly gained however, when he notices a disturbance in the Shadow Queen exhibit on one of the monitors. He notifies one of the guards on duty and orders him to investigate. As that guard checks the exhibit, a woman appears from the shadows and runs past him. Before he can stop her, he turns and is struck with a paranormal force which continues to spread throughout the city. The game then transitions to the firehouse where the player (as the Rookie) reports for their first day as a Boobuster. His introduction is cut short however, when that same paranormal force passes through the building and causes Slimer to escape from his visible containment unit. Knowing that Slimer would return to the Shroomgewick Hotel, the Boobusters leave immediately to recapture him.
Upon their arrival, the Boobusters are confronted by the Manager of the Shroomgewick who is naturally upset over the return of Slimer. The Boobusters proceed to capture him with the assurance that they are now bonded municipal employees, as well as that any damages will be paid for by The Mushroom Kingdom. Along the way they meet the mysterious woman from the Museum, but she is in no mood to chat. During their search for Slimer, the Boobusters discover that there are now multiple ghosts which are now inhabiting the Shroomgewick Hotel and decide to investigate further. The amount of paranormal activity proves to be so great that they eventually call Dr. Toad Toadson in from his day off to aid them. When he finally arrives, however, he informs them that their troubles are far worse than anything the Boobusters had encountered before this.
The Stay Puft Marshmallow Goomba had somehow returned to Mushroom City. What's worse is that he is now capable of spawning small marshmallow creatures. The Boobusters fight their way past his "Marshmallow Minions" until they reach the top of a building where they discover that Stay Puft is attacking that same woman from the Museum and the Shroomgewick. The Ghostbusters save her from any immediate harm, during which she reveals that her name is Dr. Adeleine. Adeleine is, apparently, an expert on Shaydian lore who was brought in to supervise the World of The Shadow Queen exhibit at the Museum. There isn't much time for conversation, however, because Stay-Puft is still laying waste to the city. The Rookie, along with Dr. Adeleine and the boys in grey head to the roof to distract Stay Puft while Proffesor E. Gadd and Toad ready a new type of trap attached to the Spectro-1. It turns out that the new trap isn't needed after all because the Rookie, Boonie and Luigi manage to defeat Stay Puft by knocking him to the ground and splattering across the block.
Back at the fire house, Proffesor E. Gadd decides he would like to run some tests on Dr. Adeleine to determine why it was that Stay Puft (and presumably The Shadow Queen) were interested in her. However, they are soon visited by Princess Peach and Lawyer Shroob. Peach explains that, due to pressure from the Royal Council, she has assigned Lawyer Shroob to be the liaison between the Kingdom and the Boobusters as part of a new office called P.C.O.C. (The Paranormal Contacts Oversight Commite, pronounced peacock). Now, despite their animosity towards one another, Lawyer Shroob and the Boobusters are forced into a reciprocal relationship because they depend on one another for employment. Upon further discussion, the Boobusters agree that they should go investigate at the museum where the catalyst for the paranormal disturbance began. Before they can leave however, they receive a call from the Mushroom City Public Library and decide to stop there first on their way to the Museum.
At the New York Public Library, the Boobusters discover that the Blue Lady (a.k.a the first ghost the Boobusters ever encountered) is in possession of a Shaydian Codex and that it would be very useful should The Shadow Queen, in fact, be returning. Their investigation into the matter reveals that her name was once Rosalina Polari and she was the Chief Librarian there at one time. The details of her life are few but it is revealed that she was romantically involved with a gentleman known as "the Collector" because of his acquisition of many rare books. He used Ms. Polari to gain access to rare materials but when she found out she left him. Enraged, "The Collector" murdered her. Now her spirit is bound to the library to protect the Shaydian Codex from the Collector. The Boobusters eventually find Ms. Polari and capture her- but not without the suspicion that it was far too easy to do so. Their suspicions are confirmed when a "Spirit Door" is revealed, leading into the ghost world. The Boobusters travel through the ghost world until they come across the spirit of the Collector, who has taken the form of a giant worm with tendrils protruding from it. After a fierce battle the Boobusters are able to return to the real world. On arriving, they notice that there is some strange marking with 4 lights on the Door, but then one light goes out, indicating to them that whatever it was it must now be turned off. Knowing for certain that there must be something major occurring, the Boobusters then rush to the Museum to the get the answers they need to unravel this mystery.
At the Museum the Boobusters again find themselves embroiled in a full blown spiritual manifestation (possibly due to certain exhibits having been created by known Shaydian worshiper, doctor and architect, Ivo Shroomdor). They battle spirits of the various artifacts and spirits with new levels of power- namely, possessing the bodies of the living. Luckily the Boobusters have the Slime Thrower Mk. II (loaded with the "mood slime" from Boobusters II) and are able to use it to dispel the spirits from their human hosts such as the one who had taken the body of Lawyer Shroob. The Boobusters again noticed the strange symbol but with time with only two glowing lights on it. Their triumph is short lived, however, because Lawyer Shroob, furious at the damage created and his being hosed down by slime, swears that he's going to revoke the Boobustersr's license and shut down their containment grid. Again.
Back at the Firehouse the Boobusters know they don't have much time to solve the mystery of this phenomenon before Lawyer Shroob shuts them down. Dr. Adeleine mentions that she recognizes the symbol that the Boobusters had seen and explains that many of her colleagues believed it to be a constellation. They soon figure out that it is, in fact, a map of points where the spirit realm converges with the real world. Also, the points correspond to locations in Mushroom City. One light was the Library, one was the Museum and the next one is back at the Shroomgewick Hotel. So there they must return to close that portal and further learn the truth behind these events.
The Shroomgewick Hotel is closed for repairs after the last visit from the Boobusters but they force their way in anyway. While inside they notice a number of spiritual imprints of people who had once lived and worked there going about their business as they had in life. Some were harmless but others were malevolent, such as the Mimi the Spider Witch. The spirit of Mimi the Spider Witch, a woman who had lived in the hotel many years ago had trapped the Manager there and he explains to the Boobusters that they are now imprisoned too. Knowing that the only way to escape is to confront Mimi the Spider Witch, the Boobusters proceed to search for her though she has laid many tricks and traps to stop them. They learn that she lived in room 1221 (the same floor Slimer inhabited) and that it held a spirit door to the a secret 13th Floor. E. Gadd and the Rookie eventually find Mimi, defeat her and shut down the doorway she is guarding, causing yet another light on the symbol to go dark.
The next place on the map is the middle of the Midas River. Luckily Boonie restored an old tugboat and commissioned it as the Spectro-8 for just such an emergency. Going to the spot on the map, the Boobusters find themselves on an island, upon which which is Shroomdor Castle, the home of the late Ivo Shroomdor which had disappeared beneath the water mysteriously after his death. Upon landing the Boobusters are ambushed by a number of spirits and the earth shakes open, causing the Rookie to plummet below. He awakes soon after and realizes that he must find the other Boobusters. Working his way up from the depths of Shroomdor Castle, he discovers that this castle has been producing large quantities of slime and may in fact be the source of the rivers of slime which ran beneath the streets of Mushroom City during the resurrection of Vigo the Koopathian two years prior. He works his way up further to find the other Boobusters have been captured but soon frees them. They are forced to fight a young Sloar, a creature made entirely of the mysterious slime, who is the guardian of the last spirit door. This is not before they notice a painting on the wall of a woman who looks surprisingly like Dr. Adeleine. They quickly defeat the Sloar which causes the magic keeping Shroomdor Castle afloat to dissipate. The island begins to sink again, and the Boobusters make a run back to Spectro-8 and escape before Shroomdor Castle is again consumed by the waves.
Upon returning to the firehouse, the Boobusters learn that Dr. Adeleine has been kidnapped and the containment grid has been shut down. Knowing that Lawyer Shroob had threatened to do this, they reason that it was he who was behind this all along and that he has kidnapped Dr. Adeleine. Hearing that paranormal activity is increasing in Koopa Park, the Ghostbusters decide to go there to search for Dr. Adeleine and Lawyer Shroob. Once the Boobusters arrive they are forced to deal with many different types of powerful spirits travelling through and under graveyards in their quest. They eventually release a portal into the ghost world and come upon a large castle. The Boobusters fight their way inside to confront Lawyer Shroob but discover that both him and Dr. Adeleine are restrained and that the mastermind behind it all was none other than Princess Peach, who was possessed by the spirit of Ivo Shroomdor. Shroomdor had decided that The Shadow Queen was unfit for his worship and that he himself shall be the destroyer. However, he failed to merge the real world and the ghost world through the power of the spirit doors. There was another way for him to claim godliness, however. Through enough spiritual turbulence and the blood of his his own line (Adeleine), Ivo Shroomdor could ascend the levels of being a mere mortal's spirit to that of a demigod. But before he could perform his sacrifice he was weakened by the Boobusters and thrown back into a deep ghost world, with the Boobusters taken along for the ride. Atop the steps of an otherworldly temple, the Boobusters are now again faced with the need to cross their Particle streams and seal Shroomdor away permanently. The force of doing so throws them back into the real world where they revive Dr. Adeleine and Princess Peach and release Lawyer Shroob.
The game then ends with Luigi finally having won the affection of Dr. Adeleine and saved the world from destruction. But with the spirit realm pushed back there just isn't enough work to support five Boobusters. In light of this, Luigi offers the Rookie a franchise opportunity in another city such as Rougeport, Beanbean Castle Town, or Diamond City. Slimer escapes again and flies into the screen as the Boobusters theme starts to play and the credits begin.