Hoffel continuously fails to kill the Chanels. Chanel #8 tips Hoffel off that the swamp water is highly explosive, giving Hoffel an idea to use the swamp with a bomb to kill them. She unplugs the cryogenic chamber that Denise is in in order to plug in machinery used to drain the swamp.
Cassidy is unable to bring himself to kill #3. He resolves to speak to his mom about stopping the killing. #3 and Cassidy have dinner with Jane, but Jane refuses to see reason and stop the killing. She disowns her son and storms out. Cassidy tells #3 that Hoffel is the other Green Meanie and warns her that Hoffel might have something big planned.
Meanwhile, Hester convinces Brock to marry a dying Dean Munsch so that they can inherit her money once she dies. Hester intends for them to use the money to purchase Blood Island, so they can hunt down and murder tourists there to satiate their homicidal urges. Brock agrees and marries Munsch, much to Munsch's delight and Chanel's horror.
#5 figures out that Munsch might not have Kuru shortly after the wedding and convinces Brock to do a brain biopsy to test for it. Hester attempts to convince Brock to kill Munsch during surgery to ensure they get the money, but Brock refuses.
In the well, Zayday talks sense in Jane Hollis, convincing her to stop her vendetta against the hospital. She brings Jane to the hospital to show her that it actually heals people and doesn't kill them.
During the biopsy, Chanel plots to spill a piping hot Pumpkin Spice Latte in Munsch's open brain in an attempt to kill her, but ends up missing. The biopsy goes smoothly, but the tests are inconclusive. #5 deduces that extreme dehydration might be causing Munsch's issues, and Munsch realizes that she does not, in fact, drink anything but scotch and vodka. Munsch calls her old Papua New Guinean travel companion, who confirms that she actually ate lamb brain, not human brain. Munsch is confirmed to not have Kuru and not be dying.
In celebration, Hoffel convinces everyone to go down to the basement. Once there, she traps the Chanels, Brock, Munsch, and Cassidy in a cage. She holds them at gunpoint and then reveals that she's Agatha Bean's sister, though the Chanels don't initially remember Mrs. Bean. #3 reveals that she saw Hester packing her suitcases into a car and heading for the airport, explaining why she isn't in the cage with them.
Jane and Zayday arrive to stop Hoffel. Hoffel shoots Jane and locks them both in the cage with the others, where Jane dies in her son's arms after telling him he would have made his father proud. Hoffel reveals her bomb and then leaves them to die. Denise miraculously wakes up, healed, and saves the day by disarming the bomb.
The group escapes and runs after Hoffel. In the pursuit, Hoffel throws a machete at Chanel #3, but Cassidy jumps in front of it, sacrificing himself to save #3. Cassidy dies and the chase continues, until they find Hoffel having fallen into a quicksand pit in the swamp. The group initially votes to allow her to die, but Munsch's conscious prevails and Munsch attempts to save Hoffel. The rescue attempts fail, and Hoffel drows in the swamp.
In a voiceover, Chanel explains everything that happened in the aftermath. #5 enjoyed success as an "Idiot savant" in all things medical at the hospital. Zayday and #5 were left in charge after Brock and Munsch left the hospital separately. Hester drained Munsch's accounts by posing as her at the hospital, using the money to abscond to Blood Island with Brock, where they lived like kings with a butler and hunted tourists. Munsch sold the hospital for a fortune and became a sex therapist for women in their '50s.
Chanel becomes the doctor-host of her own doctor talk show "Lovin' the C," with #3 as her executive producer, having learned literally nothing from her experiences. She leaves the studio at night and gets into her car, where she finds a Kappa Kappa Tau pin and the Red Devil waiting for her in the backseat.