When the Venture Family visits Tijuana for a lecture Dr. Venture is giving at the (community) University of Mexico, the dastardly Monarch weaves a cocoon of villainy that leaves the Venture Brothers trapped in his clutches, Dr. Venture kidney-less and Brock...dead? If only Dr. Venture would return his calls...
The Venture Family must travel to space to repair an orbiting space station that Dr. Venture's father built in the 1970s, but a mysterious space phantom could be haunting the station! This gets even more intense as Brock's presence adds heat to an already tense romantic relationship between the station's two officers.
To protect the Venture compound while Brock is on his yearly mountain survival sabbatical, Dr. Venture builds a panic room and a robotic bodyguard--which are soon put to the test when both the Monarch's and Baron Ünderbheit's henchmen choose the same night to launch attacks. While the supervillains bicker over who has dibs on Dr. Venture, Brock is busy befriending the strangest couple in the Cascadian mountains, and H.E.L.P.eR. runs away in a fit of jealousy.
Dr. Venture is offered a job by theme park owner and cartoon magnate Roy Brisby, who won't take no for an answer in his quest for worldwide entertainment dominance. Meanwhile, the boys are given the Patty Hearst treatment by the Orange County Liberation Front, a group of militant suburbanites who want to take down Brisby's empire. Brock enlists the aid of former lover and fellow superspy Molotov Cocktease to "mount" a rescue, but she may have her own agenda.
Dr. Venture's new experiment has the entire family interested--not to mention trapped inside! The Ventures' strange new neighbor, master of mysticism Dr. Orpheus, may be the only one who can help them escape. Meanwhile Dean falls for Dr. Orpheus's teenaged daughter and Brock has an encounter with his old flame, Molotov Cocktease.
On a scientific expedition in the Bermuda Triangle, Doc's experimental equipment awakens and possibly enrages the submerged ghost of Major Tom, a test pilot who crashed in an experimental aircraft designed by Doc's father. While there, the Venture's hydrofoil is hijacked by a group of fake ghost pirates who've been stranded in the Sargasso since Jesus Jones was popular.
Dr. Venture, Pete White and Master Billy Quizboy are invited to take part in a top secret government think tank run by supergenius Professor Impossible (coincidentally their former college professor), but Doc's life is in jeopardy once he learns the dark secrets of Impossible's sequestered family. Meanwhile, Hank has become a walking time bomb thanks to a stolen Cold War serum, and Brock and Dean are in a race against the clock to save him.
The Monarch sends Dr. Girlfriend undercover to seduce Dr. Venture in order to inject him with a body-altering serum. Meanwhile, Brock is deeply depressed to learn his secret agent license to kill has expired, but the boys are hell-bent on helping him cram for his government exam.
The Monarch finally has the Venture family right where he wants them--hanging upside down above the Amazon river! But his victory is postponed when Dean suffers a strange ailment: according to the bylaws of the Guild of Calamitous Intent, a temporary truce must be called in order to get Dean medical attention, so Brock and Hank are held as collateral. Doc calls on his friends, Master Billy Quizboy and Pete White, to help Dean with his mysterious ailment.
Always short on cash, Dr. Venture decides to unload some of his father's old scientific equipment in a huge yard sale that attracts fellow scientists and super-villains alike. Everyone is supposed to be on their best behavior, but the Monarch can't resist the temptation to wreak havoc once he finds himself inside the "belly of the beast"...and in desperate need of a bathroom.