Timmy Turner and Jimmy Neutron become bored with their very easily outmatched competition, so they team up and create a villain to fight. Their villain won't be evil and refuses to destroy him. Eventually, he does in turn attack Retroville from feeling neglected after Timmy and Jimmy abandoned him. Jimmy fights back with a J tank but their villain then adapts to stop it because Timmy wrote adaptable as one of its powers instead of adoptable. Then the villain attacks Dimmsdale and rids all of the fairies of their power and steals Jimmy's intelligence! Then, their new villain known as Shirley is attacking them nonstop. They then trick Shirley into going into Retroville to search for Jimmy and Timmy, but soon after they find Shirley putting citizens of both worlds into his own, alternative world like where he was born in.
Shirley now has taken over both worlds and is planning his revenge against Timmy and Jimmy for abandoning him like that.
Jimmy builds a new portal alongside his friends Carl and Sheen, and uses it to discover that Timmy is coming to Retroville to see Cindy. The two boys fight until they find that Cindy is out of town, whereupon they decide to become best friends and ditch their friends. After defeating Jimmy's enemy, Eustace, along with his Tripod, and beating the Crimson Chin's arch-enemies, they believe they can make a great team, so they create the greatest evil villain, named Shirley, but he doesn't turn out evil, just clueless and stupid. As Jimmy and Timmy try to find ways to make him "the greatest villain of all time," including golf bar hits that throw him from Dimmsdale into the Palace of Westminster in London and the Leaning Tower of Pisa, they become more and more annoyed until finally they abandon him at a mall to work on a new villain. At this point, Shirley realizes he has been abandoned and turns evil. He chases after Timmy and Jimmy, who fire lasers at Shirley, and then find out instead of typing in "Adoptable" into the computer which created Shirley, like Wanda had suggested, they had typed in "Adaptable," as Shirley deflects their attacks with "anti-laser bracelets." After the fighting gets out of hand, and Jimmy and Timmy become bored with the evil Shirley, they hit the button to self-destruct Shirley. Realizing he's about to be destroyed, Shirley reaches inside of his robotic body and tears out a small bomb, which he hurls into the air seconds before it explodes. Angered even more by this, Shirley captures the two, absorbs Jimmy's brain and Cosmo and Wanda's wands, steals one of Jimmy's inventions from his universe, and opens up a new, totally blank universe between the two, becoming close to an all-powerful god in the new universe. Shirley starts to take things from both Timmy's universe and Jimmy's universe, causing holes to open and swallow everything into a void. As both universes fall apart, residents from both universes are kidnapped into the new universe (which is in 2D), populated by objects stolen from the other two universes. Sensing that they are unhappy at the prospect of living in a bland world, Shirley tries to help them, but Timmy and Jimmy pair back up with their friends, who take advantage of Shirley's low intelligence to make him give up his adaptable powers, his weapons, etc. They do this by trapping Shirley under a butterfly net, rendering his magic useless and forcing him to give Cosmo and Wanda their wands back. At this point, the now-restored fairies, at Timmy's behest, are able to negate Shirley's super strength, and he becomes crushed by a car when trying to throw it. When the others attempt violence on the weakened villain, the two boys explain everything. After the universe is restored, Shirley becomes an unconventional pizza restaurant owner, and Jimmy gets his brains back, but not before Cindy forces Jimmy to say "You're smarter than me" a number of times.