The opening scene begins with an assassin known as The Chemist, who has an injured Werewolf trapped in a circle of mountain ash while he works on an altered virus. Meanwhile, at the McCall House, Scott and Stiles listen to a cassette tape they found in Garrett's bag of Deadpool money, which has instructions from The Benefactor on how to participate in the Deadpool. Confused by the instructions, Scott and Stiles discuss what to do with the $500,000 in cash they stole from Garrett; Scott argues that the money belongs to the Hale Family, but Stiles doesn’t want to give Peter his money back. Before they decide anything, Malia shows up, giving them just enough time to hide the money under Scott's bed before she makes it to his room. When Malia rushes in, she quickly informs them that, though she and Derek found Satomi Ito's pack, most of them are dead.
Derek takes the badly-injured Braeden to the hospital, where he immediately shouts that she had been shot and needs medical attention. Outside of the Beacon Hills Animal Clinic, Deaton is in the process of locking up when he's confronted by a hooded person. The two engage in a fight, with Deaton using a retractable steel baton while the other person fights with a steel spike. When a crack of lightning illuminates the assailant's face, Deaton realizes that it is Satomi, whose Werewolf eyes glow Alpha red.
The following morning at the school, The Chemist, whose first name is Simon, is one of the proctors for the PSATs, which are being taken by Scott, Stiles, Kira, and Malia, as well as the rest of their junior class with the exception of Lydia, who took it as a freshman. When Simon asks about the second proctor Natalie Martin informs him that Coach Finstock is supposed to be helping her, but he hasn’t shown up. When she goes to look for him, she finds him slumped over his desk in his office, leading her to initially believe that he had passed out drunk and that he had relapsed after fifteen years of sobriety from alcohol.
However, after Sydney, a fellow junior, briefly passes out during the test, Natalie notices that she has a rash forming on her wrist and realizes something bigger is going on. She then goes to Coach Finstock's office a second time and checks to see if he is developing a rash as well, which she finds to be the case when she lifts up the back of his shirt and notices to her horror that he has a pustule-rash all over his back. Believing there to be a smallpox outbreak, Natalie frantically shoos a group of teenage athletes out of the school, fearing them contracting the virus as well before she calls the Centers for Disease control. The CDC quickly shows up and, upon confirming the spread of a virus, decides to quarantine the school until they can figure out what is going on.
At the animal clinic, Deaton is examining one of Satomi's Betas, Reed Schall, who has succumbed to an illness which has caused him to lose control over his transformation and begin to bleed black blood from his eyes, nose, mouth and ears. Satomi describes to Deaton the symptoms of the illness, which eventually progresses to blindness and eventually a rapid death. Meanwhile, at Beacon Hills Memorial Hospital, Melissa McCall, having heard of the viral outbreak, goes to visit Braeden and Derek in Braeden's hospital room, giving the latter naloxone to counteract the pain medication they gave her so that she can ask her questions about what she witnessed with Satomi's pack. Though Derek believed the Werewolves to be poisoned, Braeden informs them that they were actually infected with a specific virus created for the sole purpose of killing Werewolves.
At the Martin Family lake house, Lydia has brought a box of Meredith Walker's belongings to the Banshee study, where she lays out the few possessions Meredith had at Eichen House (a nearly-empty bottle of perfume, a bouquet of dried white carnations, a teddy bear, and a photograph of Meredith) in front of her and turns on the record player in order to listen to the black record and attempt to speak with Meredith's spirit. She tells Meredith that she's sorry that she couldn't help her and laments the fact that she doesn't have better control over her Banshee powers, which she wishes she could use to save everyone on the Deadpool. When Lydia gets no response, she sighs in defeat and gathers up Meredith's things, only to become shocked when she realizes the photo of Meredith was taken in the very study in which she's standing.
At the school, the students are lined up to have blood samples taken in order to analyze the virus to which they've been exposed. While they wait, Malia asks Kira, afraid that Malia will find out that she is actually aHale and Peter's biological daughter due to Malia being listed as "Malia Hale" on the final portion of the Deadpool, tries her best to distract Malia from the topic. When it's Kira's turn to get her blood drawn, her inner Kitsune spirit releases a spark of foxfire that shocks the CDC clinician, burning a small hole in her protective suit.
Scott, Stiles, Malia, and Kira all go to Coach's office with Ken Yukimura, who notices that they’re all sick in one way or another: Malia's claws have extended and will not let her retract them; Scott's claws and fangs, and glowing eyes have been extending and retracting against his will; Kira's neurological function (specifically her hand-eye coordination) began rapidly deteriorating; and Stiles became pale, sweaty, and weak and had begun developing a rash on his wrists as well. Realizing their symptoms put them at risk of exposure to the human population of the high school students and could potential cause them to lose control over their transformations, the gang and Ken decided they needed to be quarantined from the quarantine and chose the Hale Vault as the most secure location in which to sequester themselves.
The pack was successful in finding a secondary entrance to the vault, but, upon realizing that only Malia, as a Hale, could open the vault door, Scott and Stiles lied and stated that Malia was the only one who could open it because Scott couldn't get his claws to extend. Malia, realizing that the three were hiding something from her, informed them that she would only open the vault after they told her their secret. When Malia then guessed that they were trying to hide the fact that she was on the last portion of the Deadpool hit-list, Scott and Stiles, relieved, informed her that she was indeed on the list for $4 million. Malia seemed satisfied by this reaction, stating that with Kira worth $6 million and Scott worth $25 million, the assassins would be more likely to go after them first, which embarrassed Stiles, though he argued that this was still progress for her.
One the four settled in the vault, Stiles brought up the fact that their current location was where the Deadpool began, as the Benefactor's minions had used the $117 million stolen from the vault to fund the hit-list. They went on to discuss how that much money could change their lives, with Stiles concerned for his father, Noah, who was drowning under the pressure of the bills from Stiles' stay at Eichen House and Beacon Hills Memorial Hospital, and with Scott concerned about his mother's struggle to pay the bills through working countless double-shifts. The conversation then turns to the concept of bearer bonds and how they have become obsolete in the modern day, with Kira wondering aloud how the bonds could be converted into cash.
Eventually, Scott and Stiles step aside to discuss their other problem-- the fact that they need to tell Malia the truth about her real father. Scott is in favor of coming clean about their knowledge of this information, whereas Stiles is afraid it will push her away from them and drive her right to Peter. He’s also afraid what Peter will do to her once she confronts him, as he's sure Peter will manipulate her, just like he manipulates the rest of them, and that it would cause him to win and them to lose.
When Scott overhears several teachers wondering about their whereabouts upstairs, they decide Stiles has to leave in order to keep them distracted, and because he won’t be affected by the virus like the canine supernaturals will. Meanwhile, at the hospital's morgue, Deaton and Melissa perform an autopsy on Satomi's recently-deceased Beta, leading Deaton to figure out that they're dealing with the canine distemper virus-- specifically, one that has been weaponized through genetic engineering to target and kill canine shapeshifters.
Back at the school, Stiles figures out Coach is the only adult who had been infected, so he begins searching his office to figure out the source of his exposure. Meanwhile, at the hospital, Satomi reveals that she’s a longtime friend of Derek's mother, Talia Hale, and during their conversation, Deaton figures out that Satomi’s love of wild purple reishi tea inoculated her from the virus, which means it could possibly be used as a cure as well. Derek then realizes that his family kept a jar of it in the Hale Vault-- the same jar Kira was looking at during the pack's conversation about bearer bonds.
In the Hale Vault, Scott, Kira, and Malia's condition has worsened; Scott and Malia are bleeding black blood from their mouths, nose, ears, and nail-beds, and both Kira and Malia have gone totally blind, leaving Scott with only partial vision due to his Alpha immune system.
Miraculously, all of mundane humans in the quarantine begin to recover from their symptoms, with the supernaturals in the Hale Vault only getting rapidly worse. The Chemist confronts Stiles in Coach's office once he figures out that everyone was exposed to the virus through the ink pad used for thumbprint identification and aims a gun at his head. He wants the location of his friends so he can get "visual confirmation" of their deaths and get paid by The Benefactor. Stiles refuses to give up the location of his friends, but before The Chemist can pull the trigger, Agent McCall shoots the assassin in the head, and then gives Stiles a message from Melissa-- the antidote, reishi mushrooms, is in the vault.
Scott barely gets to the tea in time, but he finds the strength to pull it from the shelf and break it open, allowing himself and the others to breath in the cure before it can finally kill them.
Unfortunately, as Scott, Kira, and Malia get better, their eyesight returns, allowing Malia to see that she's listed on the last portion of the Deadpool list, which she found in Stiles' coat pocket, as "Malia Hale." When Stiles tries to comfort her, she swats his hand away from her and walks out of the vault without another word, clearly upset by the secret Stiles and the others had kept from her.