Conan O'Brien hosts the "series finale" of The Simpsons, in which the finale itself is generated by an AI machine called HackGPT. In the finale, Bart's 11th birthday approaches and he realizes that Springfield is changing around him: Principal Skinner leaves for Sacramento with Groundskeeper Willie, Mr. Burns passes away and his fortune is given to the power plant employees, Comic Book Guy and his wife Kumiko's baby is born, with John Cena assisting with the delivery, Moe's Tavern closes, Nelson's father and the real Seymour Skinner return, Krusty the Clown ends his show, and Chief Wiggum joins the Chicago Police Department, as well as various marriages and deaths. Bart gains sentience within the finale and tries to resist the changes.

The Simpsons go to a fancy resort intended for Springfield's elite for a vacation, thanks to Homer buying timeshares back when Marge was pregnant with Bart. But when they discover he was scammed and are thrown out only 20 minutes later, the family squat in a room designated for the luggage of a rich newly-wed named Tasha, whose new husband is Sideshow Bob.

Sick of hearing Lisa complaining about Springfield, Marge sends her off with Patty and Selma to Capital City. There, Lisa meets some of the city’s urbane artists who invite her to join them at a party where like-minded individuals gather. Lisa decides that this culture is her future instead of Springfield and is swept away into a surreal journey through Capital City’s art and drama scene only to soon discover things aren't as they seem.

The Springfield Police Department unearths a coffin with two corpses in it that also contains a business card of Grampa Simpson’s from the 1980s during his brief stint as a private investigator. While Grampa tries to avoid his past, a curious Lisa pushes him to reopen the cold case that caused in the disappearance of his partner Billy and involved both Agnes Skinner and Mr. Burns.

A series of scary stories are prefaced by "Cottage of Terror", a Mexican-themed opening animated by Jorge R. Gutierrez:

• "The Information Rage": Bart and Lisa find themselves having to put their differences aside as built up political divisiveness and rage manifests as two giant monsters and it’s up to the Simpson siblings to save Springfield.
• "The Fall of the House of Monty": On the day after Thanksgiving, Victorian-era Mr. Burns becomes a victim of his own greed and cruelty as the dead workers from his corn syrup factory rise up and seek revenge on their former boss.
• "Denim": In a parody of Venom, Homer comes into contact with a pair of sentient extraterrestrial denim pants that quickly bond with him, only to refuse to leave him when he needs it the most.

Guest stars: Juan Carlos Enriquez, Jorge R. Gutierrez and Tim Yoon sing "Jarabe Tapatío" and Rob LaZebnik as Spit-Takers Anonymous Guy

An assortment of stories involving the female residents of Springfield like Luann Van Houten, Malibu Stacy, Mrs. Muntz, Marge, Patty and Selma, Bernice Hibbert, Mama Risotto, Lunchlady Dora, Lisa, Agnes Skinner, Helen Lovejoy, and Rayshelle Peyton. Parodies include Barbie, West Side Story, The Nanny, and The Chronicles of Narnia: The Lion, the Witch and the Wardrobe.

In an ode to the works of Ray Bradbury, the Simpson family attend a carnival where Lisa meets an individual known as The Illustrated Man who uses his tattoos to weave various stories for her.

• A 1950s Bart hears what he thinks are the screams of a woman buried alive in the woods only to discover nobody will believe him.
• A retro-future version of Superintendent Chalmers is convinced by Carl to use a replacement robot duplicate of himself to avoid spending time with Skinner.
• Homer is part of a law enforcement team set in a police-state future Springfield where consuming any media that isn't considered as prestige television is illegal.

Guest star: Andy Serkis as Siegfried Blaze and The Illustrated Man

The Simpsons mention at a Congressional hearing about the time when they were trapped on a flight with the most unruly passengers in America, some of which they know. They soon find that each of it's passengers are slowly disappearing.

Animosity between Marge's sisters Patty and Selma and Homer peaks when he ruins Patty and Selma's birthday escape room experience. Meanwhile, Krusty is told by his Aunt Sadie Krustofsky to stop being an elitist celebrity and connect with his crew. When Aunt Sadie's tough love approach gets her Aunt Sadie own personal improvement show, Marge uses it to try and bring Homer and her sisters together as well as some other people.

Mentalist Derren Brown comes to Springfield to bring some Christmas cheer back to the town. He unintentionally makes Homer believe he is Santa. When Flanders becomes jealous of Homer's celebrity, he has a crisis of faith.