When Billy and Mandy's school is preparing for a big game, Mindy entrusts the care of the school's mascot, Fluffy Cat, to Billy, to protect him from being kidnapped by the rival team, the Booty Heads. At Billy's house, Fluffy Cat is a disaster, so Billy's mom throws him into the basement, where the cat gets inside Grim's trunk, absorbing its powers. A giant Fluffy Cat appears just before the game wreaking havoc.

While at Sassy Cat Land, the theme park dedicated to Sassy Cat (and to ridiculously long lines), Billy, Mandy, and Grim stumble upon a closed attraction, a futuristic "house of tomorrow". Inside, they find Master-Control, a sentient and autonomous, thinking, feeling artificial intelligence computer program claiming to know everything (and wishing death upon the trio when Billy angers him), and Tom Smith, a tour guide that became trapped in the house when it closed forty years ago. Tom explains that the attraction closed when a kid, actually Billy's dad, annoyed Master-Control with his dumb questions, and the robots started attacking the humans. Billy, Mandy and Grim exit the house unharmed, but Tom misses his opportunity to escape and is left behind again.

After a trip to the mall, Mandy becomes the spokesperson for Happy Huggy Stuffy Bears, a new stuffed toy in town. After the success of her commercial, Mandy gives away stuffed bears to other children, who start wreaking havoc in the city. Eris, the goddess of chaos, is behind the toys, which mind-control the children into creating chaos. Mandy decides not to share control of the world with Eris, and orders Grim to destroy the toys.

When Grim misuses his powers to play bowling with asteroids, he is taken to the Underworld court and sentenced to 50 hours of community service. At a retirement home, Billy, Mandy, and Grim go to the supernatural wing, which is the Home of the Ancients, a place for retired, geriatric monsters. Grim meets his childhood idols, the Bride of Frankenstein, Dracula, and the Wolf Man. Despite Billy's comments that the old monsters are finished, Grim sets out to prove that they are still scary. Grim tries to scare a bunch of kids in the woods, but the old monsters ruin his attempt and he walks out on them.

The day before Christmas, Billy, Mandy and Grim go to the shopping mall, where Mandy complains that Santa Claus is just an invention from corporations. Grim assures Mandy that Santa is real, and they even went to college together. They decide to travel to the North Pole and meet Santa, but when they arrive Mrs. Claus tells them that Santa Claus has been transformed into a vicious vampire.

There is a new student in the school, named Dora (parodying Dora the Explorer), who insists on getting people to open her lunch box. Mandy befriends Dora once she gets into a fight with the snobby Mindy. While noting something strange with Dora, Grim does not recognize her as Pandora until it's too late and she tricks Mandy into opening Pandora's box, releasing all kinds of plagues upon humanity. Mandy restores everything to normal, and captures Pandora inside the box, saying that nobody tricks her, and that when the time is right it will be Mandy herself who will unleash humanity's doom and destruction.

When Billy destroys Grim's favorite childhood toy, Fancy Jake, Grim feels devastated and wishes he had never lost the limbo game that made him become Billy and Mandy's best friend forever and ever. A lawyer appears saying that although the game is legally binding while all parties remain on Earth, it is not if Grim leaves Earth. In consequence, Grim follows the lawyer's advice, opens a mystical portal, and leaves. With Grim traveling aboard his spaceship, the lawyer takes off his disguise and introduces himself as Morg, the Martian Grim Reaper, who is also Emperor of Mars and commands an army of Martian, brain-eating zombies.

A scene of Endsville two weeks into the future shows a dystopian world ruled by the "Lord of Horror", who wields the all-powerful artifact known as "Horror's Hand". At the same time, two robotic replicas of Billy and Mandy are sent into the past, to stop the real Billy and Mandy from interfering with the current events.orror's Hand to rule the world.

When Billy is sent to bed after playing with his Dr. Brainiac action figure, he wishes he had an adventure. He notices a strange light outside and wanders into a corn field to investigate; he encounters Sperg, and both of them got caught by a UFO's tractor beam. Inside the extraterrestrials decide to experiment on them.

As Billy, Mandy, and Irwin need to write a school report on tall tales, Grim tells outrageous tall tales about Pecos Billy (based on Pecos Bill), Paula Bunyan (based on Paul Bunyan), and John Henry. In Grim's stories, Pecos Billy (Billy) tames a twister using his personal laser-shooting cow-like spacecraft, saving an Arizona trailer park; Paula Bunyan (Mandy) uses her blue ox companion, Babe, to stomp over a villain, creating the Grand Canyon in the process; John Henry (Irwin) digs through a tunnel so fast that he breaks the laws of physics and bursts into the "eighth dimension". After Grim tells them the stories, Mandy informs Billy and Irwin that he is trying to get them F's.

When Grim cannot take any more abuse from Mandy, Billy tries using Grim's scythe to shrink her to mouse size. Instead of shrinking, Mandy becomes a giant and destroys Billy's house. Although Mandy enjoys being a giant for a while, there are inconveniences, as she keeps growing as time passes, and she wants to return to her normal size. Billy is the only one who can cancel the curse he put on Mandy, and he refuses to do so. Mandy grows bigger than the planet, and she finds herself in the "Realm of the Infinite" with other creatures that grow at infinite pace. Mandy starts bossing them around to please her.

When Billy's dad drives Billy, Mandy and Grim to the hamburger restaurant, they somehow end up in Mexico. There, the people are celebrating Dia de los Muertos, but local kids say it may be the last celebration ever, because Del Uglio, a masked and ugly luchador, is set on stealing the "Golden Nose of Chipotle", a prehispanic relic on which the festivity is based. To get to the nose, Del Uglio has one half of the map, while the other half is held by his lost twin brother, who turns out to be Billy. Grim defeats Del Uglio, but it is Mandy who keeps the golden nose for herself, which makes her rich.

When Billy starts taking pictures with a camera found in Grim's trunk, Grim tells him that is an Underworld's True-heart Camera, which shows the real essence of a person's heart. When Mandy takes Irwin's picture, it is revealed that he is actually half-good and half-evil. Irwin explains that although he was born evil, his dad taught him about love and respect, and he had a change of heart. Upon knowing this, and against her own wishes, Mandy also experiences a painful change, turning good and kind-hearted. Mandy and Irwin finally share a romantic kiss in this episode, but it makes Mandy revert to her old dark and sinister self, which was Irwin's true intention, as he likes her just the way she is.