Following the devastating impact of COVID-19 in "The Pandemic Special", South ParQ citizens now try to get vaccinated against the disease. The vaccination location is Walgreens. Many adults queue for the vaccine but the security guard does not let them in as vaccinations are reserved only for seniors above 55 and first responders. The elderly mock the townsfolk after getting vaccinated, and go out to party and drink to celebrate. This angers the townsfolk even further.
Meanwhile, the conspiracy theory group QAnon tries to stop people from getting vaccinated. This is because they believe in the existence of the Hollywood Elites, a secret cabal of Satan-worshipping, pedophilic cannibals. The elites are said to insert nanotechnology microchips into the vaccines so as to track and manipulate the masses.
The teachers at South Park Elementary are extremely frustrated about not being able to get vaccinated. Mrs. Nelson is replaced by Mr. Garrison after she is pranked by the boys. They want to get her back, so Mr. Mackey tells them to steal vaccines from Walgreens and bring them to the teachers.
The boys show up outside Walgreens dressed as healthcare workers accompanying a wheelchair-bound elderly woman. They claim to be the Kommunity Kidz who assist elderly people who need help in getting to their vaccination locations and are let in. Their plan takes a downturn however when the elderly woman claims to have forgotten that she had been paid for her role, demanding payment from the boys once again. She ultimately reveals the truth to the pharmacist attending to them. Realizing that their cover had been blown, the boys resort to kicking the pharmacist and stealing the vaccines before making their escape.
The boys call Mrs. Nelson from Cartman's house, telling her to come to school the next day for the vaccine. A crowd of townsfolk show up and try to convince the boys to give them a shot. The boys promptly escape to the now-deserted Raisins where they spend the night. Cartman tries to get people to bid for a shot, Stan suggests they take the vaccine themselves, while Kyle is pressured by his dad to give his parents the vaccines. The next morning, he tries to replace some of vaccines with Cactus Cooler and is caught red-handed by Stan.
As they approach the school to bring the vaccines to the teachers, they are stopped by the Lil' Qties, the children's arm of QAnon, who have been brainwashed with their beliefs. A fight ensues and the boys escape to a bridge and unsuccessfully try to get the teachers to meet them elsewhere for the vaccination.
After a discussion about their failing broship, the boys go back to the school and prepare to fight through the crowd to get in. The townsfolk clamoring for the vaccines are there, so are the QAnon members and Lil' Qties trying to stop the vaccinations. However, Garrison shows up, interrupting them. He has worked out a deal with the Hollywood Elites to bring in enough vaccines for the whole town from Israel. The townsfolk are ecstatic and start vaccinating themselves on the spot. With the path clear, the boys enter the school with the vaccines for the teachers. However, they are too late; Mrs. Nelson has been infected with COVID-19 and dies from it.
At her funeral, Father Maxi congratulates the townsfolk for having survived the pandemic. They all start to party because they have been vaccinated and think they are immune to the disease. On Main Street, two men even spit into each other's mouths to celebrate the end of masks and social distancing. Walgreens has now become lame as everyone has been vaccinated.