Set ten years after the events of Attack of the Killer Tomatoes (referred to as the "Great Tomato War"), the United States is once again safe, and tomatoes have been outlawed (although authorities still deal with "tomato smugglers" who sell to people who cannot live without ordinary tomatoes). Wilbur Finletter (Steve Peace) has been praised as a hero of the Great Tomato War and parlayed his fame into opening Finletter's Pizzeria, which serves tomato-less pizzas. Working for Wilbur is his nephew Chad Finletter (Anthony Starke) who is a delivery boy. Also with Chad is his roommate Matt Stevens (George Clooney), a suave ladies' man.
However, trouble returns with a misanthropic villain, Professor Mortimer Gangreen (played by John Astin) and his assistant Igor (Steve Lundquist - who also is an Olympic swimming gold medalist) seek to unleash another wave of tomato terror. Professor Gangreen was perplexed at being defeated by "Puberty Love", the worst song ever created, and says that this time music will aid, rather than hinder him. Gangreen has created a tomato transformation chamber by which he can turn ordinary tomatoes into replicas of men and women. By dipping ordinary tomatoes into vats of toxic waste and then placing them into the chamber, Gangreen uses music to his advantage, as the juke box that is hooked up to the chamber syncs up with the tomato transformation chamber, allowing him to create virtually anything by the use of whatever song he has picked (Michael Jackson music seems to make tomatoes into a clone of Jackson, the Miami Vice theme seems to make replicas of Don Johnson and seductive music apparently turns tomatoes into beautiful women). Gangreen's preferred music is rock, which creates soldiers. With his tomato commandos, Professor Gangreen seeks to attack the nearby prison where he will break out his imprisoned ally Jim Richardson (Rick Rockwell), then take over the United States under the subjugation of his killer tomatoes and installing Richardson as President of the United States. Gangreen has also used his device to create an attractive female replica named Tara (Karen Mistal), who serves Gangreen (as she straightforwardly informs a visitor: "I'm his lover. I also cook and clean.") until she realizes his abusive attitude towards a wrongly mutated tomato whom she dubs FT, or Fuzzy Tomato. Tara defects to Finletter's Pizza where she starts dating Chad.
The quirky plot line partially breaks the "fourth wall" as the characters relate to the audience that the production has run out of money. Matt suggests "product placement" – at that time an emerging practice in film and television – as a solution for the financial problems. From that point forward, the film's characters comically showcase and promote various products as the film's plot line continues.
Chad and Tara have a whirlwind romance where everything seems to be going magically except for Tara's strange behavior and extreme aversion to any form of music. Chad's dislike of tomatoes eventually causes a rift between himself and Tara and after an extremely caustic remark at a romantic dinner Tara dumps a drink in Chad's lap in retaliation. While Chad is in the bathroom cleaning up a violinist comes by and begins to play for Tara, who changes back into a tomato. Panic ensues and the restaurant empties as the other patrons flee in terror at the sight of the tomato. The sound of a chiming grandfather clock turns her back into a human as Chad returns to the now-deserted restaurant and they leave.
Tara continues to protect FT while living with Chad (and Matt). Chad notices the garbage truck Igor is driving while Igor tries to find Tara and follows it to the dump (where Igor picks up more toxic waste) and back to Dr. Gangreen's house where Chad watches as they transform a tomato into a person.
Going home Chad finds Tara consuming plant food—they both scream and she runs away, only to be kidnapped by Igor and returned to Dr. Gangreen. Chad, who has found a tomato at a grocery store he believes to be Tara, returns with Matt to use Dr. Gangreen's equipment to restore the woman he loves. They find the machine can create a wide range of people depending on the music used, including more beautiful women (of great interest to Matt) but they do not get Tara back. They are captured by Dr. Gangreen who squishes the tomato and has Igor throw Chad and Matt into the dungeon.
There they find Tara undamaged and in human form and she and Chad reconcile. Outside the locked door they hear FT, to whom they pass a message that FT is to deliver to Wilbur who gathers the team of heroes from the first movie to rescue the captives. But while they are en route Dr. Gangreen forces Chad and Matt into the transformation chamber and starts a countdown that at the end will transform the two into tomatoes. He and Igor then leave with a captive Tara to raid the prison and start Dr. Gangreen's plan for world domination but Wilbur and his team rescue them just in time.
At the prison Dr. Gangreene transforms a bag of tomatoes into a massively-muscled and well-armed assault team and they storm the prison. While fighting Tara breaks away and Gangreen and Igor chase her, who are in turn chased by Chad, Matt, Wilbur and the others. They find Gangreen and Igor have imprisoned Tara in a gas chamber and threaten to gas her if the pursuers do not surrender. Also Igor has a hand grenade. In the ensuing fight FT throws himself on the live hand grenade before it explodes and Gangreen successfully triggers the gas. As the fumes envelope Tara behind the door she and Chad have a tearful farewell and it appears Tara is finished. Matt presses a button to clear the gas from the chamber.
A distraught Chad opens the door to find an unharmed Tara; she isn't human so the gas didn't hurt her. Dr. Gangreen triumphantly plays music to transform Tara back into a tomato but nothing happens; exposure to the gas has made Tara permanently human. The town celebrates the heroes again, including and especially FT, as people wonder where Matt went and it is remarked that he returned to Gangreen's lab to destroy it but he instead is using the equipment to produce beautiful women. The credits role and we hear over the soundtrack the hosts hate the movie and an army of killer carrots kill them by shooting them.
