Years after the murderous events at Kappa House, Dean Munsch purchases an abandoned hospital under the guise of fixing the healthcare system in America. After recruiting surgeons, Dr. Brock Holt and Dr. Cassidy Cascade, as well as medical student Zayday Williams, the Dean shocks everyone when she enlists the services of the disgraced Chanels to join the ranks at the teaching hospital. Meanwhile, secrets from the hospital’s past begin to reveal themselves and a new killer surfaces.

The frightful events of Halloween force Dean Munsch to notify authorities of murders at the Institute, which leads to a surprising influx of new patients. Meanwhile,Chanel is tired of doing dirty work, so she concocts a plan that entails recruiting new patients to join the Chanels. Later, Zayday and Chanel #5 visit a person with ties to the hospital's past; and a new patient's problems have the staff going a bit mad.

After an influx of patents at the C.U.R.E. institute, Dean Munsch and Chanel organize a blood drive to solve the hospital's severe shortage. Meanwhile, Nurse Hoffel sets a plan of revenge in motion, Hester finds a way to join the hospital's staff and a shocking revelation involving The Green Meanie occurs.

A man from Dean Munsch's past checks in to the C.U.R.E. institute with plans to win her back, causing a jealous Brock to further question his relationship with Chanel. Meanwhile, Zayday and Chamberlain devise a plan to discover the origins of The Green Meanie killer with shocking results.

The Chanels are overwhelmed when their TV idol, Dr. Scarlett Lovin, visits the C.U.R.E. Institute. Meanwhile, Hester calls a Green Meanie summit as the killer(s) put their final kill plan into effect.

The Green Meanie sets its final plan for revenge in motion as Hester makes a bold move to secure her future, and Brock performs a dangerous surgery to save Dean Munsch's life.