In the aftermath of Catherine Hobart's murder, a detective interviews #5, who was left alive. The detective believes #5 may have killed Hobart, as do Chanel and #3, who believe that #5 might have murdered Hobart because she was jealous about the two of them going out on a double date with the doctors.
A new patient, Tyler, arrives at the hospital with a condition (neurofibromatosis type 1) that causes tumors to grow en masse all over his body. The doctors tell him that there is a very expensive laser machine which can shrink and remove the tumors, but the hospital doesn't have one. Tyler is distressed because he has no money for it.
Zayday becomes suspicious of Dean Munsch's motives in opening the hospital, becoming convinced that she did so to lure the Chanels there and pick them off one by one. She enlists Chamberlain Jackson's help to investigate. They discover that the hospital's online records were scrubbed. When they find the archived physical records, they discover that in 1986, the Green Meanie massacred the entire hospital staff -- including Dr. Mike and the nurse who murdered the patient in the premiere's flashback. They run into Nurse Hoffel, who suspiciously tries to hit up Zayday for detailed information about the Chanels' schedules.
Chanel and Dr. Holt go on their date at a movie, where Dr. Holt's mystery hand acts of its own accord uncontrolled by him -- it gropes Chanel and steals Twizzlers from another guy. Chanel believes he's imitating the guy with the out of control hand in the movie they're watching.
Chanel #5 bonds with Tyler. After discovering that Tyler was once very attractive before his condition, #5 decides to find the money for the laser to cure him.
Chanel, alone during the night watch, is accosted by someone wearing the Red Devil costume, but it's revealed to only be Chad, looking to spook her. He reveals that he's brought his friend, who needs medical attention, to the hospital and that he wants Chanel back.
Chanel, Holt, and Munsch meet with Chad and his friend Randall, who won't stop screaming at slight stimuli after accidentally shooting Liz Cheney in the face during a secret hunters society hunting trip. Holt diagnoses him with the Jumping Frenchmen of Maine disease, an exaggerated startle reflex, brought on by shooting Liz Cheney. Munsch promises that, though the disease is supposedly incurable, they'll help Randall.
#5 makes a terrible fundraising video to raise money from Tyler. Chanel and #3 suggest that she start dating Tyler while he's still deformed so that he feels obligated to stay with her even when he is cured.
Eventually, #5 and Tyler continue to date and fall for each other. Tyler offers to help #5 find proof that she was not Hobart's killer. #5 viciously beats up two guys who insult Tyler.
Cascade and Holt bring Chad to where they are treating Chad's friend Randall (to little avail). Chad notices Holt's hand acting of its own accord, spontaneously writing down a specific meal.
Munsch meets with Denise Hemphill for help with figuring out who the killer is. Denise still believes Zayday is the murderer. She explains that to catch a killer, you have to get inside the mind of a killer. She brings Munsch, Chanel, and #3 to the prison where Hester is imprisoned. Hester somehow knows all about the Green Meanie and its attacks, but refuses to help until the group gets her a transfer to their hospital and procures some high-end discontinued beauty products.
Chanel and #3 cruelly congratulate Tyler on being able to look past #5's faults and love her. Chanel explains that she got the money for the laser from Chad.
Chad grows increasingly jealous of Chanel's relationship with Holt, challenging the doctor to a squash match. Holt is suspiciously good at squash and threatens Chad to stay away from him and Chanel. Later, Chad has an investigator look into Dr. Holt. The investigator uncovers the fact that the donor hand was from a notorious serial-killing squash player who murdered the opponents that lost to him.
Zayday researches Munsch's condition, eventually having a breakthrough when she realizes that Munsch previously visited New Guinea and accidentally ate deceased human flesh. She explains to Munsch that she was infected by the diseased corpse brain she ate and that she only has a year to live. Munsch begs Zayday and Chamberlain to keep it a secret, not wanting the board to think she’s unfit to run the hospital. Hoffel, who has been spying on Munsch, overhears this information.
Tyler and #5 have a Facetime chat the night before his surgery. He is about to tell #5 what the Encyclopedia Brown fandom found out in researching the Green Meanie case when someone enters the room and wheels him away for surgery. #5 panics and runs to the hospital with Chanel and #3. There they find Tyler brutally murdered by the Green Meanie. #5 is distraught that her one and only chance for happiness is gone. Chanel notes that they have another killer on their hands.