The Venture Compound is under seige as Nazis hold Dr. Venture hostage, while newly hired Venture bodyguard Sgt. Hatred must help Doctor Orpheus deal with a dog containing Hitler's DNA that Dean has adopted. Meanwhile, Brock Samson recovers from a near fatal injury and must join forces with a long forgotten enemy, SPHINX, to stop Molotov Cocktease and Number 21 seeks Dr. Venture's help to clone a new Number 24.
The Monarch attempts to hold Hank and Dean for ransom, but his plan is foiled by the arrival of Monarch's other arch-nemesis, Captain Sunshine. Sunshine recruits Hank to become the new Wonder Boy, complicating Monarch's scheme to collect his ransom.
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.
Number 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.
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.
Dr. Venture's therapy group, a collection of former Boy Adventurers (who have become failed adults), quickly fall back into their old habits when a mystery is literally dropped into their session. Meanwhile, Sgt. Hatred tries to overcome his own past when he's stuck in a movie theater crammed with kids. History is doomed to keep repeating itself if Hatred and Dr. Venture can't break their cycles.
The Order of the Triad must banish and destroy a demon spawned from hell... While the Order of the Triad battle a Hellbeast, Triana accidentally stumbles into another plane of existence.
21 seeks revenge on Brock Samson for the murder of 24. Meanwhile, the Monarch has a sinister plot to finish off Dr. Venture once and for all...