Four millennia ago a cult was formed to worship the dead god Dormazu the Destroyer, and to pray that he stayed dead. Today the last member of the cult lays dying, and with his end will come the reawakening of Dormazu. Who do you call when ancient gods threaten the world? Not the Ghostbusters; they're taking the day off. This time the world will have to be saved by a team of untrained, unassisted, and underpaid rookies.
Ghostbusters: Sanctum of Slime is a four player co-op twinstick shooter. Players must defeat hordes of ghosts in each room before eventually reaching the boss of each level. Each Ghostbuster is equipped with three proton streams, red, yellow, and blue, and the correct color must be switched to to defeat ghosts of a similar color. In addition each stream can produce effects on some enemies even if they are a different color: red slows enemies, yellow causes them to pause, and blue bounces off of obstacles. Stronger ghosts can sometimes leave behind powerups like double damage or bonus points. Points are awarded for chaining together defeats of ghosts, destroying property, or reviving teammates. In addition to the normal walking levels there are two levels where the Ghostbusters ride in the back of the Ecto-4WD, and must defend the vehicle from attacking ghosts. If less than four players are present AI will fill in for the missing slots.