The single-player campaign is the same for the Xbox 360, Windows, and PlayStation 3 versions of the game. The Wii and PS2 versions have a significantly different campaign, but the stories are mostly identical.
The game is a third-person shooter, placing players in the role of a new recruit to the Ghostbusters team known as "the Rookie". Players control the Rookie's movements as he explores the environments of each level, seeking out paranormal activities and ghosts, either alone or in conjunction with the other Ghostbusters. Players can switch to a first-person perspective by equipping the Rookie with a PKE Meter and goggles. In this mode, paranormal items are highlighted and the PKE Meter helps direct players to ghosts or haunted artifacts.