This version is different from its DS and GBA versions. The story has Crash's arch-nemeses, Neo and Nina Cortex, creating a device that turns the creatures on Crash's island into monsters, threatening to bring an end to existence on the peaceful island. Crash must stop them by "hijacking" these monsters and wield their power against the Cortex's.

The gameplay has the player explore levels, picking up power-ups to use against enemies as well as for the first time, use fighting combos such as punches and kicks against enemies. Players can also "hijack" 15 different enemy monsters to use against the others, each with their own special abilities and powers like fire breathing and earthquakes. Players can also interact with their world, climbing trees and swinging from ropes and even surf and skate throughout the levels. There is also co-op abilities where a friend can pop into the game at any point.

The games across are almost identical, excluding controls (the Wii utilizes the Wii-remote) and graphics are different depending on the systems graphics capabilities.