A cross between Space Invaders and Bust-A-Move, Monster Bomber requires players to use the lower window and stylus to generate colored balls to power-up and fling at monsters shown on the upper screen. Gamers must hit colored monsters with balls of the same hue, while avoiding such obstacles as walls and black holes. However, powering up balls of any color can knock monsters into each other and blow all of them away.

Knocking out monsters with combos fills the rainbow meter faster, initiating a short period of multi-colored balls that destroy all five unique monsters without discrimination. Gameplay features single-player "Scenario" and "Survival" modes, and wireless play for up to four players. "Scenario" mode is a 20-stage challenge with multiple objectives, while "Survival" mode keeps the enemies coming until the player dies.