Mario, a Puerto Rican and Mexican American living in Austin, Texas, learns that his four-year-old daughter, Anita, has acute lymphoblastic leukemia. The doctors note that Hispanic children have statistically lower cure rates. Mario has possessed a lifelong supernatural gift, a sensitivity to premonitions and whispered warnings, but he received no warning about Anita's illness, which fills him with rage. As Anita deteriorates, Mario loses his job due to excessive absences. Medical bills pile on top of existing debts, and an experimental treatment remains out of reach without adequate insurance.
Desperate, Mario contacts Brian, a former coworker who now uses meth and deals drugs. Brian gives Mario a gun, a photograph, and an address, instructing him to kill a man for $6,000. Mario drives to the location and shoots the man in the back of the head. Driving back to Austin, he receives a call from his wife, Melisa, who is screaming and crying. He understands immediately: Anita has died while he was committing murder.
Grief consumes them both. Five weeks after the funeral, during an argument, Mario's anger erupts. He shoves Melisa, elbowing her in the face and sending her crashing through their kitchen table. Instead of helping her, he locks himself in the bathroom. The next morning, she is gone, leaving a note that she is moving to her parents' home in Orlando. Mario signs and returns the divorce papers the following day.
Alone and spiraling, Mario hallucinates: tiny footsteps outside Anita's room, a bleeding girl who vanishes when he reaches for her. Over the following months, he kills four more men for Brian, finding that the violence numbs his grief and gives him a grim sense of purpose.
Brian then calls with a different proposition promising retirement money. At Brian's house, Mario meets Juanca, a former driver for the Juárez Cartel. Juanca explains that internal turmoil within the Sinaloa Cartel has made its cash shipments from Houston back to Mexico vulnerable. The plan is to intercept one such truck, kill the crew, and take the money, with support from the Juárez Cartel's leader, Don Vázquez, who will provide a mysterious weapon. Each man's cut will be $200,000. Mario agrees, driven by the prospect of paying off Anita's medical debts and winning Melisa back. Brian's pregnant girlfriend, Stephanie, expresses relief that Mario is joining.
Before reaching the border, the group makes a horrifying stop in San Antonio. In a dilapidated house, an old woman named Sonia, El Milagrito's caretaker, amputates a toe from El Milagrito, a boy with severe disabilities whose body parts have been sold to cartel members who believe they carry supernatural protection. Juanca pays Sonia with Don Vázquez's money and takes the wrapped toe. Mario is horrified but does not intervene.
During the drive to El Paso, three white men at a barbecue restaurant hurl racist slurs at Mario and Juanca. Brian stays silent. Outside, Juanca beats the most aggressive man and later berates Brian for his cowardly silence. When Brian steps away, Juanca privately warns Mario that Brian plans to kill him after the job to increase his own share. Mario also discovers gruesome photos in the glove box showing a mutilated man with severed feet.
In El Paso, they stay with Juanca's elderly mother, Margarita, who gives the men a blessing. She has already lost two sons to cartel violence and begs Juanca to be careful. Privately, she warns Mario that Brian is greedy and that if Mario is not careful, Brian will kill him.
They cross into Mexico through a tunnel beneath Margarita's kitchen, encountering dark, inhuman creatures clinging to the walls. In Ciudad Juárez, they visit El Imperio, Don Vázquez's club and cockfighting venue, where they meet La Reina, whose real name is Jessica Kayden King. She is a tall, blonde, trans American woman who serves as Vázquez's ruthless second-in-command. Vázquez receives the wrapped toe and conducts a supernatural ritual: His men gut a bound prisoner named Rodolfo alive over a pool of crocodiles, and a blind, handless old woman named Gloria, a bruja, or witch enslaved by Vázquez, extracts a gray substance from the corpse. Vázquez applies this substance to the men's foreheads as supernatural protection. Rodolfo's body is sealed in a metal box and placed in their truck. At a church on the Mexican side, Mario learns that Juanca is also seeking revenge for his brother Omar's murder, a motive Juanca has kept hidden.
Back at Margarita's house, Mario overhears Brian on the phone saying what sounds like "three ricks." He later connects this to "three bricks," meaning $300,000, which is $100,000 more than Brian's agreed-upon share. Combined with Juanca's and Margarita's warnings, Mario concludes Brian intends to steal his cut and decides he must kill Brian first. He and Juanca arrange a signal: After the job, Juanca will send them both to retrieve boxes from the truck bed, giving Mario his opportunity.
They collect a loaded Ford F-150 from Steve and Kevin, two gun runners near the New Mexico border who will also serve as hilltop snipers during the ambush. That night in the Florida Mountains of southern New Mexico, the snipers disable the Sinaloa Suburban. A chaotic firefight erupts. Brian is shot in the leg but keeps fighting. Juanca opens the metal box, and Rodolfo emerges as a reanimated, ravenous corpse, impervious to bullets and weeping even as he kills. He charges the cartel men and tears them apart.
In the aftermath, Juanca gives the signal. At the tailgate, Mario sees Brian reaching toward his waistband, where he customarily keeps his gun. Mario recites a prayer and shoots Brian in the head. They stab copies of Omar's death photo into the cartel corpses as a message of revenge. Juanca finds approximately $2 million in the Suburban.
Back at El Imperio, Don Vázquez divides $600,000 between Mario and Juanca, including Brian's share as a bonus. La Reina hugs them both, crying; Mario realizes she was Omar's romantic partner. Vázquez gives Mario a small figurine of Santa Muerte, a folk saint personifying death, and tells him to find his wife. They return through the tunnel to the US and drive to Austin.
At home with $300,000, guilt over Brian's death overwhelms Mario. He puts a gun in his mouth but cannot pull the trigger. Then he finds Brian's gun still lying in the back seat of the car. The realization crashes over him: Brian is unarmed when Mario shoots him. Brian is reaching for his pants because his belt is tied around his wounded leg, not reaching for a weapon. Mario has killed an unarmed friend based on lies.
Driven by obligation, Mario takes a backpack of cash to Brian's house to give Stephanie the money. Stephanie opens the door without asking about Brian. Juanca emerges from the hallway, barefoot. Mario understands the full betrayal: Juanca and Stephanie were romantically involved. Juanca has manipulated Mario into killing Brian through fabricated warnings so he could claim Stephanie, Brian's money, and eliminate a rival. Mario pulls his gun, but Stephanie shoots him twice, in the back and the stomach. They take Mario's $300,000 and leave.
Bleeding heavily, Mario drags himself to the wall. He pulls out his phone and, instead of calling 911, calls Melisa. The call goes to voicemail. A shadow figure appears and transforms, revealing an image of an elephant in a tutu, connected to Anita. Mario looks up, ready to see the face of God. The novel ends here, his fate unresolved.