Six years after the conclusion of The X-Files, former FBI agent Doctor Dana Scully now serves as a staff physician at Our Lady of Sorrows, a Catholic hospital in Seattle. There, she is treating a young boy named Christian, who suffers from Sandhoff disease, a terminal brain condition. Suddenly, FBI agent Drummy arrives, seeking Scully's assistance in locating Fox Mulder, the ex-leader of the X-Files division, who has gone on the run. He promises that the manhunt for Mulder will cease if Scully helps investigate a series of mysterious disappearances of women, including young agent Monica Banan.
Reluctantly, Scully agrees and manages to persuade Mulder, who has been living in isolation, sporting a beard and obsessively clipping articles about the paranormal, to assist. Despite his initial concerns that this is a trap set by the FBI, Mulder joins Scully in the investigation.
The duo travels to Washington, D.C., where they meet Agent Dakota Whitney. She seeks Mulder's expertise on the paranormal, as they have received a lead from Father Joe (played by Billy Connolly), a defrocked priest with a sordid past of pedophilia who claims that God is sending him visions connected to the crimes. While Mulder is inclined to believe Father Joe's revelations, Scully is repulsed by his history and dismisses his insights.
Things take a dark turn when, during a chilling visit to the home of the kidnapped Banan in snowy Montana, Father Joe unexpectedly begins to bleed from his eyes while praying. Later, another woman becomes a victim, as she is forcefully abducted by Janke Dacyshyn, a notorious snowplow driver.
As the investigation continues, Scully and Mulder find themselves entwined not only in the case but also in a personal discussion concerning their past and the son Scully gave birth to, William. Their emotional connection deepens as they uncover that a severed arm connected to the case has traces of an animal tranquilizer, further motivating Mulder to delve deeper into the investigation.
Following an arduous night search, Father Joe leads the team to a frozen burial ground revealing grisly evidence of numerous victims. This deeply troubles Scully, who admonishes Mulder for his obsession with the dead — reminding him that he cannot change the past regarding his own sister's untimely death. Despite this, Mulder presses on, motivated by Father Joe's admonition not to give up.
As evidence points them toward Dacyshyn, the team faces setbacks, including a tragic betrayal leading to Whitney's death during a raid. Meanwhile, Scully struggles with an ethical conflict at the hospital, fighting for permission to perform an experimental procedure on Christian against the wishes of the hospital head.
Scully's crisis reaches a peak when she confronts Father Joe regarding his visions. In a moment of despair, she learns that Father Joe suffers from advanced lung cancer and holds what may be the key to Banan's fate.
Despite their complex relationship, Scully advises Mulder to step back from the case for fear of dragging themselves into a dark path, while Mulder persists in searching for Dacyshyn independently. A fateful confrontation ensues, leading to a harrowing rescue where Scully saves Mulder from certain doom.
In the aftermath of all their tribulations, Scully learns of Father Joe’s passing, and Mulder draws unsettling connections between the timing of his death and that of Tomczeszyn. The emotional toll weighs heavily on Scully as she grapples with her role in Christian's potential surgery. In a moment of clarity, she resolves to move forward, building on the mantra of resilience she learned from Father Joe: "don't give up."
In a whimsical post-credits scene, we see Mulder and Scully together in swimsuits on a boat, leisurely rowing towards a tropical island, a shimmering reminder of hopes and possibilities still to come.
