Stimpy has invented a wondrous, diabolic machine... The Mutate-O-Matic! Unfortunately it explodes, and having pieces of a Mutate-O-Matic lying about is not a good thing. So Ren and Stimpy embark on an adventure that spans Mr. Horse's refrigerator, to the pound, and even... The Great Outdoors! References from the cartoon are frequent, coupled with lots of side-scrolling action.

Players can switch controls between Ren and Stimpy. Their respective abilities vary greatly, even though they tend to use each other for their moves (i.e. Stimpy uses Ren as a boomerang and Ren uses Stimpy as a bowling ball).

Another player can also jump in at anytime and play as either Ren or Stimpy.