Ghostbusters II is played from a side-view perspective across linear action stages. The player controls a Ghostbuster, moves through city and supernatural environments, avoids hazards, and uses the proton weapon to deal with enemies and ghosts.

Objectives vary by stage but generally involve reaching the end of an area while surviving attacks and environmental obstacles. Progression is level-based rather than experience-driven, and failure typically requires replaying the current section. The DOS version is a single-player action game with no documented multiplayer mode.

Stay mobile rather than trading contact damage with enemies. Fire at ghosts from a safe distance and learn the timing of recurring hazards before advancing.

Conserve lives by treating each stage as a pattern-learning exercise. When a section seems crowded, prioritize the nearest threat and use the available space instead of rushing toward the exit.