This episode was originally going to be the last episode of season 16, but was held over after FOX decided to air "The Father, the Son, and the Holy Guest Star" (which was temporarily banned following Pope John Paul II's death).
The title is reminiscent of the 1956 movie The Man Who Knew Too Much starring James Stewart and Doris Day, and more recently, the 1997 movie The Man Who Knew Too Little starring Bill Murray. This is not the first time this title has been parodied; see "The Boy Who Knew Too Much" and "The Dad Who Knew Too Little".
The book The Land of Wild Beasts is a parody of Where the Wild Things Are by Maurice Sendak, right down to the artwork.
The stamp museum sign "The Fathers (and mothers) of Invention" is a reference to Frank Zappa's first band, The Mothers of Invention.
The Simpsons visit a stamp museum featuring stamp posters of Frederick Ives, Katharine Burr Blodgett, Alexander Graham Bell and Elisha Gray, with audio statements about their inventions.
The advertising campaign Bart and Lisa watch in the theatre mentioned above is for a restaurant called "The Hillside Wrangler", a parody of Kenneth Bianchi and Angelo Buono who were called the Hillside Stranglers . Part of the Eisenhower Expressway is also called the Hillside Strangler .
When Lisa finds Dr. Nick in the cemetery, he puts four severed arms around his body and says: "I'm not Dr. Nick, I am Dr. Octopus!", a reference to Dr. Octopus, the super-villain of the Spider-Man series. Also, he speaks some lines referencing the series, mentioning Spidey (Spider-Man) and Mary Jane Watson. The comment about the upside down kiss references the 2002 Spiderman movie.
During the Itchy & Scratchy cartoon, Scratchy attends the musical Cats and finds the show so boring that he shoots himself in the head.
Lisa says she learned from Scooby-Doo that the only thing to fear are crooked real estate developers. This is a reference to the show's frequent plotline of the ghosts not being real, but staged by unscrupulous individuals for financial gain—for example, lowering property values in order to buy up real estate at a bargain price and later turn a profit by developing and reselling it.
The song in the beginning is "eve of destruction" by Barry McGuire.
Binky from Matt Groening's "life in hell" is seen in the itchy and scratchy cartoon.