Bart and Homer are carving pumpkins and Bart slices a smile into Homer's pants. Homer chokes him, so Bart puts a flaming pumpkin on his head. Professor Frink then introduces the show, giving a warning about the content and telling those concerned to skip forward. He skips forward too far and says that he has ruined the show for everybody. He points the remote at himself until he dies and turns to dust. This blows away to say "Treehouse of Horror XXI". The monster picks up the remote and mentions The Office. This leads to a parody of the opening, set in the monsters work place.
Marge, worried about Bart playing violent video games, encourages him and Milhouse to play the boardgames in the attic. They discover a game called Satan's Path and play it, causing all the board games to come to life in a different reality. They have to complete the games to win, which results in a game of Mouse Catch.
Later Bart decides to only play hangman (thinking it would be safer). Then it is shown that Bart and Milhouse have been hung.
Homer and Marge set sail on a second honeymoon, but they're interrupted by a castaway, whom they rescue. Roger was a chef on the Albatross who was knocked out after trying to prevent an attempted poisoning on the ship. Convinced that Roger poisoned the passengers and is plotting to murder them after seeing a dead shark with a recently made pie pan in its mouth, Homer and Marge take matters into their own hands as they seemingly kill Roger and knock his body overboard. However, finding the Albatross, they realize Roger was telling the truth. Roger appears again and Homer kills him, and the surviving bankers, shocking Marge, who eats the poisonous pie.
It would all turn out to be Maggie's imagination. Homer soon asks what Maggie thinks and Marge replies that it's nice things. Soon Maggie sinisterly changes into Alex DeLarge whilst eerie music plays in the background as the screen goes dark.
In a spoof of Twilight, the Teen Vampire book and film series by Stephanie Meyer, Lisa falls in love with a mysterious new student named Edmund (Spoof of Edward Cullen). After saving Lisa from a bus and other approaching objects, Edmund reveals himself to be a vampire. Lisa is not frightened by this and the two spark a romance much to the dismay of Milhouse, who turns into a were-poodle. Marge invites Edmund and his father Dracula to dinner. Edmund and Lisa are both embarrassed by their fathers and decide to leave resulting. Homer and Dracula father track them down to a cathedral in "Dracula-la Land." Lisa wants to become a vampire, but has second thoughts after learning that she would be eight years old forever. Edmund says that "the blood-lust is upon him" and he has to bite something. Edmund and his father reconcile, and Homer saves Lisa by offering himself up in her place as the two vampires feast on him. However, they both die from the bad cholesterol in Homer's blood as he is turned into a vampire. Transforming into a bat to fly home, Homer's fat causes him to fall. His body is carried off by were-poodle Milhouse while Lisa watches in dismay. Most of these things happen in the Twilight.
Daniel Radcliffe, the main star of the Harry Potter franchise, guest starred in the third segment which parodies the Twilight novels and movies. Radcliffe said that he is a fan of the show and guest starring is "a huge honour." Hugh Laurie guest starred in a segment that parodies Dead Calm.
The episode was up 23% in viewership compared with the previous episode, "MoneyBART," which aired October 10.
The episode received mixed-to-negative reviews. Us Weekly said: "the three oddball tales run from mildly amusing to flat-out inspired. In one goofy vignette, Homer and a bikini-wearing Marge pluck a scary mystery man from the sea. However, watching Lisa crush on a brooding vampire in a dead-on poke at Twilight is the hilarious treat here."
USA Today said about the episode: "It is possible that The Simpsons has worn out the Treehouse franchise. The three installments just seem to be reaching for jokes that aren't there, and falling in the attempt. As you'd hope from The Simpsons, the segments all boast a few clever moments that will make you smile if not laugh. But they're not scary, they're not particularly funny, and outside of some stupid Twilight jokes, they're no longer even trying to be real parodies of the original stories."