Earthworm Jim gets squashed by a cow, leaving him dazed and confused. In the aftermath, his marbles go missing, so he must travel into his brain to find them and put everything right again. The gameplay is similar to that of the previous titles but takes place in a 3D environment.

America's favorite super-hero is back! This time he's fighting to save HIS OWN MIND! The wacky worm is back in a massive 3D search for sanity. Four brains to navigate. Five evil bosses to battle including: Professor Monkey for a Head, Psy-Crow, Bob the Goldfish, and Fatty Roswell. 13 weapons including the Groovy Gun, the Chicken Gun, Banana-Myte, and the good old hair flamer! 15 levels plus final mega-boss showdown! Hundreds of puzzles to solve.