Sanctum is the first book in author Sarah Fine's Guards of the Shadowlands series. The novel follows 17-year-old Lela Santos, who loses her closest friend to suicide. Lela follows her friend into the afterlife where she makes a desperate attempt to save her friend's soul.

The novel opens with Lela Santos arriving for her first day at Warwick High School. After being bounced from one foster home to the next all her life, she spent several months in a juvenile detention center after nearly killing the foster father who raped her repeatedly. She meets Nadia Vetter, a privileged but troubled girl who uses painkillers to mask her depression, and the two form a close but unlikely friendship. A year later, Lela's life has turned around with the help of both Nadia and her new foster mother, Diane, but she is crushed when Nadia, unable to deal with her depression any longer, overdoses on pills and dies. Lela, who has been plagued with disturbing nightmares since her own suicide attempt a few years earlier, begins having dreams about Nadia in a dark, dangerous city that is reserved for those who take their own lives. When she accidentally falls off a cliff and dies, Lela forgoes the peaceful Countryside and goes into the dark city to save her friend.

In the city, Lela meets Malachi, a handsome young man who is head of the guards and responsible for finding and eliminating the evil Mazikin, who steal the souls of city residents. After first mistrusting him, Lela finds herself falling for Malachi, who turns out to have a dark history of his own, having committed suicide while a prisoner in a Nazi concentration camp. Malachi has been in the city for about seventy years, but is nearing the time he can appeal to the judge and be released to the Countryside. As he falls for Lela, Malachi agrees to help her find Nadia and they are joined by Ana, another of the guards.

During their search, Lela must learn whom she can and cannot trust. She must face her worst demons by successfully navigating the city's Dark Tower that is constructed of the deepest fears of the residents. When they finally find and rescue Nadia, Lela is disappointed to find that her friend is more depressed than ever and learns that she is not capable of saving her. When they finally find themselves before the judge, Malachi and Lela both try to sacrifice themselves so the other can leave the city, but in the end both are sentenced to remain as guards but on a dangerous mission outside the city. The book ends with Lela back in Rhode Island, where many of the Mazikin have come. She is assigned to lead a special unit to find and destroy the Mazikin. She is surprised to learn that one of her assistants is Malachi, who will masquerade as a high school student as they start their new mission.