The following version of this book was used to create the guide: Tucker, Karen. Bewilderness. Catapult, 2021.

The novel opens on a February night in the fictional town of Anklewood, North Carolina, after Luce and Irene have finished their shifts at the restaurant where they work together as servers. Tomorrow, Luce will be leaving for Florida with her boyfriend Wilky to start a new life there together, so the restaurant gave Luce a small going away party which has kept them later than usual. Wilky was supposed to pick them up and give them a ride the short distance home, as the two had their licenses suspended the previous year. While the girls dig in to a junk food feast and watch late night television as is their routine, a car drives up to the house and they see it is sheriff's deputy Manny Nogales, whom Irene says she used to date until they broke up over the events surrounding Wilky's dishonorable discharge from the army. Instead, Nogales asks to come inside and for a drink of water which he loudly chugs, in obvious discomfort, before telling the girls that Wilky has just been found dead in his car in the parking lot of the var where he works of an overdose.

Irene then looks back on the time when she and Luce first met and became friends, two-and-a-half years earlier while working at the same sleazy pool hall when they were both 19. One night Irene walks into the women's bathroom at the restaurant and sees Luce being groped by a drunken patron, who Luce escapes from. After work, Irene is walking to her car when she is surprised by Luce calling for her, asking for her help with something. Irene looks into Luce's car and sees that the would-be rapist is passed out cold in the back seat, and Luce enlists Irene's reluctant help in a plan of harmless revenge, emptying his pockets and dumping him on the front lawn. Luce finds a tin of pills that she recognizes joyfully, and invites Irene to celebrate. Even though Irene had never been around such pills before, she accepts some and soon becomes addicted with Luce.

Back to the narrative present, Luce has had a sever asthma attack after hearing about Wilky, and is taken by paramedics to the hospital after given the sedative Ketamine, which concerns Irene because of its status as a drug of abuse. A day or so later, Irene finds information online about Wilky's memorial at his parents' house near Greensboro, and borrow a car even though they both have suspended licenses and are on probation for drug possession charges. They drive extra carefully and avoid main roads, and arrive at Wilky's parent's beautiful suburban home, and they feel self-conscious and improperly dressed among the well-to-do guests and family members. Luce is at first unable to find Mrs. Rowland to introduce herself and offer condolences, but manages to strike up an amiable conversation with the very drunk and sweet Mr. Rowland. Irene goes into the kitchen and strikes up a pleasant conversation herself with Wilky's sister, but when Mrs. Rowland comes in and Irene identifies herself as a friend of Wilky's girlfriend, Mrs. Rowland coldly asks Irene to leave. Before Irene can get Luce out the door, Mrs Rowland enters the room and furiously curses and insults Luce and Irene, blaming them for Wilky's disgrace and death. Luce is shocked, but curses Mrs. Rowland right back and blames her for cutting Wilky off when he needed her the most. On the ride back home, Luce makes Irene stop so she can buy tampons, which makes Irene suspicious enough to check on Luce in the convenience store bathroom to verify her claim. Irene will find out later that Luce bought heroin from the store clerk and snorted some in the bathroom, leaving her wasted for the rest of the way home.

Soon, Irene realizes that she is losing Luce to deeper addiction, so Irene gives up her 11-and-a-half months clean to join Luce in using heroin. Their 12-step sponsor Greenie comes over to insist Luce take advantage of Greenie's connections for a bed in a rehab facility, but Luce and Irene talk Greenie out of the idea and promise to join her for the meeting after a stop at Walmart. But as soon as Greenie is gone, Luce bolts out of the car to buy more drugs, with Irene in tow. They find a woman in a Walmart security uniform who introduces herself as a former acquaintance of Greenie's from the meetings, and who promises to introduce the girls to her professional connection for high-end pharmaceuticals. The girls are wary and protest, but trust the woman and eagerly anticipate the drugs they will receive, but when after waiting while, Luce gets impatient and heads to the office door.

The old doctor promises to make up for their trouble by sending the girls home with plenty of samples to avoid further trouble, and he offers them refreshments while they wait. Irene soon realizes that they have been drugged, and before losing consciousness sees an accomplice arrive and set up a camera tripod, while the doctor approaches with a dog leash. The girls wake up in a gas station parking lot, and can think of no one else to call except Teena, their old drug dealer, who arrives in no time with advice to go to the police, which the girls refuse. Instead of taking them home, Teena parks the car and takes out her heroin-injecting paraphernalia, teasing the girls about the hazards and inferiority of sniffing the drug. After some cajoling, Luce agrees to try it and her blissful reaction compels Irene to follow her, leading to an extended binge for them both, with Irene quickly learning to inject herself.

When the girls finally make it back to a meeting to pick up their one-day token, it is to a different group than their regular one with Greenie. The guest speaker is a sharp-dressing and charismatic woman who comes over to introduce herself to the girls after the meeting, with Luce confiding to her the story of recent events.The woman reveals that she is a marketing representative for a fancy rehab in Delray Beach, Florida, and that as long as Luce is still covered by her distant stepfather's insurance, she should be a shoo-in for their luxury treatment center. After Luce's insurance clears it, she is on a plane to Florida within two days, leaving Irene alone to focus on her recovery. At another meeting, Irene is approached by a teenage girl who says she has information about the actual situation in Delray Beach, a horror story of corporate exploitation where no attention is paid to the patient's recovery. After an addict with insurance is recruited for the scam, they are housed in drug-infested flophouses until their insurance runs dry. At first, Irene refuses to believe that Luce could have been a recruit into the rehab-shuffle, but cannot wait to find out for herself and so enlists true friend Nogales to drive her to South Florida, which he does with his sirens on. When they arrive, it is too late, and they learn that Luce died of a fentanyl overdose in her bathroom the weekend before. When they try to reach out to her contacts to alert them, Irene and Nogales are not able to reach anyone.