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A piece of tracing paper is put over a tombstone. When a hand starts going over it with black chalk, it reveals Treehouse of Horror XXXIV logo with cartoonish drawings of skeletonized Simpsons heads.
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Mayor Quimby announces his decision to close an art museum and convert its art into non-fungible tokens (NFTs). After sneaking inside it, Homer inadvertently digitizes Bart into an NFT, trapped in Homer's phone. After telling Marge, she enters the blockchain to rescue Bart with the guidance of "enlightened intellects" Kylie Jenner, Rob Gronkowski and Jimmy Fallon. She appears inside a train with low-value sentient NFTs. Marge's value increases as she unintentionally destroys an NFT, consequently teleporting to the following carriage with pricier NFTs.
She kills more of them, continuing through the train before reuniting with Bart, while in the real world, Mr. Burns attempts to buy Bart as an NFT from Homer. After Marge and Bart return to the museum with Jenner's key, it's revealed that Homer turned himself into an NFT during Burns' offer. The blockchain train, driven by FOMO, runs out of fuel, rendering the NFTs, including Homer, nearly worthless.
This segment begins 30 seasons ago, as the Thompson houseboat drifts to Springfield as Sideshow Bob performs H.M.S. Pinafore for a captive audience of Bart Simpson and, having wiggled to a viewing position while still in her bindings, Lisa. But right before the last note of the finale is sung, Sideshow Bob realizes he's been played. Bart only requested this performance as a means of stalling for time. Without stalling, Sideshow Bob slices Bart apart with his machete, while Lisa watches.
Traumatized ,Lisa becomes a criminal psychology teacher thirty years later. She's called upon by Officer Nelson to help investigate a series of murders with messages of the victims' names followed by "was the first" scrawled in blood. Seeking help from Bob, Lisa rejects his offers for a riddle or anagram. At a funeral, she realizes the victims were all firstborns and traces the anagram clue to a slaughterhouse owned by Ana Gram.
Nelson is killed in the slaughterhouse. Lisa discovers security footage that portrays her as Nelson's killer in a nearby room resembling her own. The police arrest her, and Lisa reveals her split personality to Bob in a cell. "Professor Lisa" was the unaware accomplice to her crimes, and Bob's guard is her sister Maggie in disguise. Lisa executes Bob, playing the same tune he sang before killing Bart, "He is an Englishman".
Homer eats a donut near the turbine room, which is not allowed. While complaining, he drops the donut at the Springfield Nuclear Power Plant and it rolls, accumulating radioactive elements and dirt, until he catches it in Mr. Burns Animal Experiments lab and he finally eats it. While near Ned, he burps a green radioactive cloud with his DNA. At a Mass, Ned finally gets the final side effects, turning into a clone of Homer, gaining his neighbor's signature fat, voice, beard and baldness, and getting an urge to watch football on TV, just like him. Ned then lets out a big burp, letting out a bigger cloud that infects everyone else at the sermon, and the virus ends up spreading quickly, soon affecting almost everyone in Springfield.
The news shows the doofi spreading. While reporting the news, Mr. Largo burps at Kent Brockman and he turns into Homer too. The three children were immediately evacuated, with Frink showing Homer what has come from his virus, a Marge-him. However, Homer actually likes the Marge-him and even celebrates living in a world of him. To make it even worse, he accidentally cuts a hole in Frink's hazmat suit with a backscratcher, exposing him to the virus too. The episode ends with Homer and all of the infected Homer clones all over the world singing Just Like Paradise, while burping.