Pinky (Rob Paulsen) and the Brain (Maurice LeMarche), two genetically-enhanced lab mice, are still trying to take over the world. However, now that they've lost their headquarters at ACME Labs, they're operating from the home of the animal over-loving Elmyra Duff (Cree Summer). Now Pinky and the Brain must continually avoid Elmyra and a neighborhood bully. Add to that a secret organization trying to apprehend the Brain. Given all of the complications, Pinky and the Brain's plots usually fail before you can say, "TROZ! ZORT!"