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.
A new patient with a hideous ailment visits the hospital in hope of a cure, but finds a love interest instead. Meanwhile, Chad returns to win Chanel back and, in the process, discovers a dark secret of Brock's. Then, after another run-in with the killer, Munsch enlists the help of new Quantico special agent Denise Hemphill.
Determined to find out who the killer is, Dean Munsch, Denise and the Chanels question Hester, as well as the sole survivor (guest star Alec Mapa) of the Halloween massacre. Chad accuses Brock of being the killer and makes a shocking proposal to Chanel. Meanwhile, a new patient with an outrageous disorder (guest star Cheri Oteri) leads Chanel #3 and Cassidy to grow closer, and another victim crashes a celebration.
After the latest attack by The Green Meanie leaves everyone shocked and saddened, Dean Munsch and Denise, along with Hester, devise a plan to catch the killer by throwing a Halloween party in the hospital. Meanwhile, Chanel celebrates a different kind of Chanel-O-Ween and attempts to make contact with the killer's latest victim from beyond the grave. Once the party begins, an outbreak surprises the hospital, leading Brock and Cassidy to jump into action, and another victim falls.
After the terrifying events of Halloween, Dean Munsch is forced to notify the authorities of the murders occurring at the C.U.R.E. Institute, which surprisingly leads to an influx of new patients. Fed up with doing dirty work, Chanel concocts a plan to put the new patients to use by recruiting them to join the Chanels. Meanwhile, Zayday and Chanel #5 pay a visit to someone with ties to the hospital's past, and a new patient's ailment causes the hospital staff to go a little mad.
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