Bub and Bob (from the arcade game Bubble Bobble) once again take the lead role in Space Bust-A-Move. Like in previous Bust-a-Move titles, the general goal of the game is to clear the screen of colored bubbles by making groups of three or more bubbles of the same color.
The game allows play in a variety of modes including Story, Versus, Endless, Challenge and Extra modes.
In Story Mode, Bub and Bob travel to various planets in search of the "Cosmo Bubbles". Each planet consists of three levels, of 5 stages each, and a boss fight stage. In each of the levels there is one Como Bubble to find and collect.
In Versus mode, the player must compete against various characters from the game. It ends either with "Game Over" or when all characters are defeated.
Endless and Challenge modes consist of bursting as many bubble as possible, either until "Game Over" in Endless Mode, or in a set amount of time in Challenge Mode.
The Extra Mode is made of many mini-games bought in the in-game shop.