Henchman 21 copes with life without 24. Brock and the Venture family are forced to part ways. Discover the final fate of H.E.L.P.eR. And Dean must kill Hitler.

The Monarch decides to settle for cash as the best revenge on Dr. Venture and takes Hank and Dean hostage. However, Hank is rescued by Captain Sunshine, who wants a new boy sidekick to replace his fallen comrade Wonder Boy.

Rusty begins to indoctrinate Dean into his career as a super scientist, not knowing that a deformed and believed aborted Dean clone stalks the compound. The deformed clone's attempt to kill Dean leads to a mix up with Hank thinking that he's killed his brother, while local police prepare to raid the Compound after a UPS delivery man suspects illegal activities going on.

Henchman 21 kidnaps the Venture brothers without The Monarch's knowledge or consent, resulting in Sgt. Hatred having to storm his former hometown of Malice to rescue his charges. We also learn of the recent activities of 21 since the death of 24.

The Guild of Calamitous Intent comes under attack by an insane Phantom Limb, who now goes by the name "Revenge". Meanwhile, Hank and Sergeant Hatred must protect the compound from the Guild's agents. We also learn something very interesting about Dean's birthright.

While Dr. Venture goes into therapy with other boy adventurers, Sgt. Hatred takes Dean and Hank to the movies, only to have a relapse.

After seeing the OutRider, the man who stole his wife, pass through the Second World, Dr. Orpheus is determined to do the same. Meanwhile, Hank takes Dean to the mall to teach him how to talk to girls, and Triana has a life-altering discussion with The Master.

While the Monarch schemes to dispose of Dr. Venture once and for all, Henchman 21 seeks revenge on Brock for the death of 24.