Crash Bandicoot X/S contains 20 levels featuring six unique locations that take Crash anywhere from the Mayan Jungle to frigid Arctic Caverns. The game also features gameplay modes ranging from side-scrolling to 3D chase levels to aerial dogfight combat sequences. The variety in presentation styles and gameplay is a hallmark of the Crash franchise and is featured throughout the game, another first for the GameBoy Advance.

In the new game, Crash will embark on a wild adventure as once again he is pitted against his arch-nemesis, the evil Dr. Neo Cortex! Orbiting high above Earth, Cortex has decided to abandon his fixation on our hero and redirect his evil focus. Why did he get into the villain business in the first place? World domination, of course! Using his latest invention, a massive shrinking ray, Cortex takes aim and fires at Earth, shrinking the planet and its inhabitants to the size of a grapefruit! Luckily, Crash's brilliant kid sister, Coco, is feverishly working on a machine to reverse the effects, but she needs crystals from around the world to power her invention. It is up to Crash to retrieve the crystals and help return the entire planet to its natural state!