Zombies Ate My Neighbors follows Zeke or Julia as they fight vampires, mummies, zombies, and other terrifying creatures to survive 50+ levels. Their goal is to destroy these monsters, rescue neighbors who have survived the onslaught, and unlock an "Exit" door that leads to the next level.
The game's setting ranges from a mall to beaches and football fields, with each level featuring its unique environment. Using different weapons such as bazooka or water gun, players must kill regular enemies and bosses to progress. Humorous elements are present throughout the game, despite its horror theme. A two-player cooperative mode allows for teamwork and adds to the game's excitement.