Timmy wishes he and Trixie were the only two intelligent life forms on Earth, besides his fairies, but soon learns that Trixie is not as easy to handle as he thought. Furthermore he cannot unwish his wish due to Cosmo refusing to let Wanda be with Timmy because he thinks she is catering to just his needs.
The students of Dimmsdale Elementary are on a field trip at the local ice skating rink. Timmy, Chester and A.J. are having fun ice skating, A.J. has enhanced training blades, while Chester is wearing nothing on his feet but socks with holes in the toes. Suddenly the announcer calls for "couples skate", and everyone begins to pair up except for Timmy, Chester, and A.J. Chester uses his "emergency couples skating kit" for just this situation, basically its a wig and a girl's dress that he puts on, him and A.J. skate off leaving Timmy alone. Timmy sees that Trixie Tang did not find a partner yet, but when he tries to get close enough to ask her, she snaps her fingers and a crowd of boys appears around her on cue, all of them commenting on how pretty she was. Chester tells Timmy that Trixie wouldn't skate with him if he was the only boy on Earth. This gives Timmy an idea, he uses his fairies to wish away all the other boys from his school, and they are all poofed away, but he is foiled again when a French foreign exchange student tries to hook up with Trixie. Timmy tries again, this time wishing he was the only boy left on Earth. However, now Mark Chang the alien tries his luck with Trixie. Frustrated, Timmy wishes that he, Trixie, and his fairies, were the only beings left on Earth, and that Trixie could not question why.
Everyone on Earth besides them is gone now. Shots of a tumble weed rolling past various famous places in the world, such as the Taj Mahal and the Great Wall of China as well as other places, revealing that Timmy's wish worked and now he and Trixie are the only humans left on Earth. Trixie finally notices Timmy and begins to show him affection, but the twitchy look in her eye reveals that being suddenly alone has taken a toll on her sanity. She demands that Timmy constantly remind her how pretty she is. Timmy obliges, ignoring her crazed laugh, and instead spending time with her. They do fun things in the empty world, like racing go-karts down the halls of Dimmsdale Elementary (Timmy's go-kart has a horn that says "Gosh your pretty" and Trixie's go-kart's horn replies "I know."), making lots of noise in the school library. Trixie is becoming increasingly demanding, constantly asking that Timmy remind her that she is pretty.
At Wall 2 Wall Mart, Trixie is sitting on top of a pile of clothes while Timmy is grilling hamburgers. Cosmo and Wanda appear as patties on Timmy's grill. Wanda warns him that Timmy should wish everything back to normal before "You know who becomes a little you know what", referring to Trixie but Cosmo thinks Wanda meant him and becomes jealous. Timmy flips Cosmo-burger over, shutting him up for a moment after a short scream of pain, and then says that he enjoys this wish too much to wish things back to normal. Trixie calls him again, and he goes to her, but notices her eyes are strained and she is becoming increasingly erratic. 2 hours later, Timmy is walking out of the boys bathroom and Trixie is waiting for him, she yells at him and believes he was in there talking to another girl. 2 More Hours Later,Timmy realizes he needs to get away from her for a bit, so he tries to hide in the Electronics department because girls hate electronics, but to his surprise Trixie appears on all the TV monitors and yells at him again, asking why he isn't wearing the sweater she picked out for him. 2 MORE hours later, Timmy is hiding behind a stack of soup cans when Trixie finds him again, whacking the soup cans away with a cricket bat. Timmy runs away from her, realizing that she has gone completely nuts with no other guys around.
While Timmy is running through the department store trying to escape Trixie, Wanda appears before him and gloats and dances around, telling him "I told you so! I told you so! Go Wanda! Go Wanda!" , Timmy realizes that Trixie is used to having hundreds of boys complimenting her every day, and with all of them gone she expects Timmy to adore her the same amount as hundreds of boys. Timmy wants to get of this relationship, so he asks Wanda to unwish the wish, but before she can, Cosmo suddenly appears. He is jealous of Timmy and thinks he is trying to steal Wanda from him, so he grabs her and they poof away. Timmy is alone, but not for long. He tries to hide in a stack of tires but Trixie was waiting right under there for him! She grabs him by the arm and drags him away, Timmy tries to gnaw his arm off but Trixie sees this and asks him why. Timmy realizes he needs to do it the hard way, and although he never thought he would do this, he breaks up with Trixie. This makes her furious, she says that if she cannot have Timmy then nobody can and, as a result, vows to kill him. Wanda attempts to poof back to Timmy so they can make a quick wish, but Cosmo jealously poofs them both away from Timmy. She chases Timmy throughout the department store, attacking him with gardening tools, a lawn mower, a baseball launcher, and even a helicopter. While Timmy ponders what they don't sell in this store, Trixie locks and says, "Even though it's technologically impossible for me to miss you, I'll MISS YOU!" and presses the fire button.
A harmless flag pops out of the missile pod, saying that the missiles were sold separately. Wanda finally manages to convince Cosmo to stop poofing them away from Timmy by hugging him and smothering him with love, causing Cosmo to realize what trouble Timmy is in, and they poof to his rescue.
Trixie instead decides to use the helicopter's rotor blades in an attempt to slice Timmy in half. Cosmo and Wanda appear in the nick of time and Timmy wishes that everyone, including aliens, were back on Earth, right in the brink of time, as Trixie's helicopter's tail rotor blade was slicing through his hair. Cosmo and Wanda grant the wish, everyone is returned, and Trixie's memory of this event was erased. Mark Chang appears in front of the White House proclaiming that he is back to dominate Earth, then quickly corrects himself and says he is a harmless girl scout when several Secret Service agents slap hand cuffs on all of his tentacles. Back at school, Trixie is her normal self now that she has her many admirers back. In the science lab, Timmy says that he is done with "couples stuff" for a while and wants time for just himself, and that he is actually glad to see other people for once. Suddenly Mr. Crocker says that it's "Romantic Lab Partners Day", he presses a button and a disco ball and flashing lights appear in the room. Chester breaks out his "Emergency Romantic Lab Partners Kit" but this time Timmy kicks him away and steals the wig from him so he can partner with A.J., who hugs the cross-dressed Timmy and whispers "Tell me I'm pretty." in Trixie's voice to him, causing him to scream in terror. Wanda and Cosmo appear nearby, Wanda says that one day Timmy will find a partner he has the right chemistry with, much like she found Cosmo. When she grabs his arms though he suddenly tries to gnaw his own arm off as the episode ends.