Booth goes missing six months after he and Brennan left their careers behind, but a case with ties to the couple pulls Brennan back into the world of forensic analysis, which brings her into contact with a member of Booth's family and Arastoo Vaziri, who's taken the lead at the Jeffersonian in her absence. Meanwhile, the FBI investigate Booth's disappearance, but one agent's tactics are bad for the team's morale.

When remains of real estate agent Justin Ross are discovered in a forest and appear to have been destroyed by coyote-wolf hybrids, Brennan enlists the help of fellow brilliant forensic anthropologist Dr. Beth Mayer to assist in the investigation. In addition to her professional achievements, Mayer is surprisingly knowledgeable about the world of fantasy football, a key link to Ross’ past and one that could provide vital information in finding his killer. As Booth and Aubrey dig into Ross’ fantasy football league history, they discover he was actively involved in a Twitter feud with NFL star Lou Divers, and was also owed a large sum of money from the league’s commissioner, making each of them suspects. Meanwhile, Brennan resists feeling competitive as Mayer impresses the team with her expertise and decades of accomplishments.

The Jeffersonian investigates the decomposing body of a social worker in the park, but evidence suggests the killer lived with the body for months before dumping it. Things get even more complicated when they determine another set of remains has similar details, which link the victims to a serial murderer who had sinister interactions with his victims' bodies. Booth and Aubrey consult with behavioral analyst Karen Delfs to help with clues to the killer's identity, while Cam tries to determine what (and who) she wants in her romantic life.

To produce a television segment on the Jeffersonian’s Medico-Legal lab, a documentary crew follows Brennan, Booth and the Jeffersonian/FBI team on a “typical” case as they investigate a corpse found in a landfill that was buried there more than a decade ago. The camera captures normally unseen footage of the team at work, while candid commentary by each of the team members provides an inside look at the investigation as Booth and Aubrey show off their unique skills in the field, and Brennan and her team prove their expertise and integral importance to solving murder cases.

The team investigates the murder of someone from Booth and Brennan's past. Meanwhile, Aubrey faces a moral dilemma of his own when he discovers his dad is back in the picture.

When a series of corpses with ties to Booth's former Army unit appear around D.C., Booth must dive into his past to find the killer before the killer finds Booth. Meanwhile, Brennan's father, Max, hides a serious medical procedure from Brennan, leaving her to grapple with her father's trust and mortality, as well as her family being in danger.