The house that old man Nebbercracker owns is alive and is swallowing whole anything that comes close to it. Three neighborhood kids DJ, Chowder, and Jenny decided to plan an attack on the house on Hallows' Eve. However, their plans go awry when police officers catch them attempting to break into the house and place the kids in the back of a police car. The house then swallows the police officers and the police car, trapping the children inside its belly.
In Monster House , players take on the role of one of the three children, exploring the house while fighting to survive. Each child has unique abilities: DJ wields a water blaster that can be re-pumped to refill it, Jenny uses a slingshot to shoot marbles at enemies, and Chowder throws water balloons to soak them. The children must navigate through the house, avoiding obstacles and finding items like keys, cans of pop to regain health, and arcade tokens to play mini-games. Saved bathrooms serve as safe zones, where players can save their progress. Scattered throughout the house are toy monkeys that unlock game art, which can be viewed in the Gallery mode.