A group of news station representatives plan to cause mass panic to increase ratings by fabricating a faux disease caused by household cats and state, among other things, that there is a vaccine available in limited supply. At the Springfield hospital, Mr. Burns steals a significant portion of the vaccine for himself, claiming that he needs to give a good example to his hounds (even though dogs are immune to the disease) and running over the rest of the vaccine with his car in the process, causing immense anger to Springfield.
After learning from his doctor that he is suffering from multiple illnesses and has only six weeks to live (even though Mr. Burns found out before that he had multiple fatal illnesses that normally would kill him, but are actually in balance with each other on the season 11 episode "The Mansion Family"), Burns becomes distraught at his fate; when he tells the news to the rest of the town, however, they celebrate and proceed to melt his ice sculpture. Realizing that no one in Springfield (aside from Smithers) likes him, Burns attempts suicide by leaping from a cliff, but ends up surviving, albeit with some amnesia and delusional behavior. Bart finds a helpless Burns in the wilderness and secretly takes him into the Simpsons' home. When Homer and Marge learn about their new house-guest, they, along with the rest of Springfield, decide to get some payback for all the misery he has caused them over the years. However, they eventually get tired of tormenting him, and cast him aside. When Lisa takes Burns back to his mansion, he regains his memory. Once again a cruel, heartless miser, he decides to put a dome over the town to get revenge on everyone who had treated him badly (inspired by Stephen King's novel Under the Dome), only to be informed that something similar was already done and it would not work again because they could simply cave their way out. (Lou even states that the only reason that they did not try it at the first time was because no one was smart enough to think of it first).
Marge tries to convince Burns that he should treat people with more respect after this experience, but her argument fails when Burns realize that is his cruelty is the only thing that has kept him alive for some time (as his six weeks have been up and he is still standing). In the end, Mr. Burns flies away in his helicopter piloted by Smithers, who at first believed Mr. Burns had died and spent a brief time working for former Vice President Dick Cheney. The two are immediately greeted by Nelson Muntz, who threatens to crash the helicopter unless Mr. Burns agrees to attend a school version of Who's Afraid of Virginia Woolf? posing as Nelson's father. Despite his disgust at being forced to watch the play, Mr. Burns actually enjoys Nelson's performance.