In a poor West Virginia town decimated by the opioid epidemic, teenagers Henry and Jane have it worse than most. Their father is Hollis Lusher, a convicted serial killer known as "the Blind Spot Slasher."

Despite being bullied and ostracized, the siblings maintain their father's innocence. But now, a popular true-crime podcast is coming to town, and their presence turns all eyes to the Blind Spot Slasher's case . . . and Henry and Jane.

Meanwhile, an eager young officer, Lieutenant Elena Garcia, is put on the case of a missing girl. Despite warnings from her superiors, Garcia begins to dig deeper into the case and realizes there may be other mysteries buried in the flood of opioid-related crimes. With many deaths quickly labeled as overdoses, or "No Human Involved," she fears the drug epidemic has created the perfect storm for a Blind Spot Slasher copycat to thrive. Unless that is, they never caught the real Blind Spot Slasher.

An amateur private investigator is also on the case: Henry's new friend, Otis. A home-schooled genius with his own family issues and a suspicion their father might be innocent, Otis makes it his mission to help Henry and Jane find the real killer. As the three probe into the evidence, they discover a possible connection between the killings and a doomsday, snake-handling cult—propelling them all down the dark backroads of Appalachia to find justice for Hollis and themselves.