Two purple birds called the Evil Twins form a new threat to Crash's homeworld. Crash has to team up with his arch rival Dr. Neo Cortex to put a stop to this new threat.

Crash Twinsanity is a classic-style Crash platform game, though this time Crash has to work together with Dr. Cortex from time to time. Crash can pick up and throw Dr. Cortex to places he can't reach himself, or use him as a hammer to slap enemies. The consistent conflict between both heroes causes many funny situations.