The human race has been taken over by small parasitic aliens called “Souls”. They travel to planets inserting themselves into a host body of that planet’s dominant species while suppressing the host’s consciousness. Deeming the humans too violent to deserve the planet, they have now almost successfully taken over Earth. The consciousness of the original owner is erased, but the Souls can access the host’s memories, and occupied hosts are identifiable by silver rings in the hosts’ eyes.
A human on the run, Melanie Stryder, is captured and infused with a Soul called “Wanderer.” Wanderer is asked by a “Seeker” Soul to access Melanie’s memories and learn the location of a pocket of unassimilated humans. Melanie’s consciousness, however, has not been completely eliminated; she and Wanderer carry out an internal conversation and debate with each other, eventually forming a friendship.
Wanderer tells Seeker that Melanie was traveling with her brother, Jamie, and her boyfriend, Jared Howe, to find Melanie’s uncle Jeb in the desert. Wanderer admits that Melanie is still present, so Seeker decides to be transferred into Melanie’s body to get the information herself. With Melanie’s guidance, Wanderer escapes and makes her way to the desert, where she is found by Jeb, who takes her to a series of caves inside a mountain where the humans (including Jared and Jamie) are hiding.
Wanderer’s presence is met with hostility by all but Jeb and Jamie. Melanie instructs Wanderer not to tell anyone she is still alive, since it would provoke them, though she later allows her to tell Jamie. Wanderer begins interacting with the humans and slowly begins to gain their trust, forming a bond with Ian O’Shea.
Seeker leads a search party into the desert. They intercept one of the shelter’s supply teams, and in the ensuing chase, Aaron and Brandt commit suicide to avoid capture. During the chase, Seeker accidentally kills another Soul, leading her superiors to call off the search.
Jared and Kyle move to kill Wanderer, causing Jamie to reveal that Melanie’s consciousness is alive. Jeb and Ian accept this, but Jared refuses to believe it until he strategically kisses Wanderer, provoking Melanie to take back control and slap him, proving to Jared that she is still alive. Kyle tries to kill Wanderer but endangers his own life and ends up being saved by Wanderer. Ian believes that Kyle attacked Wanderer and tells her he has feelings for her. Wanderer admits that Melanie’s body is compelled to love Jared, but she has feelings of her own, and the two kiss.
Wanderer enters the community’s medical facility and is shocked to discover that Doc has been experimenting with ways to remove Souls and allow the host’s mind to regain control, resulting in the deaths of many Souls and hosts. After isolating herself for several days, Wanderer learns that Jamie is critically ill with an infection in his leg. She infiltrates a Soul medical facility to steal some alien medicine, saving Jamie’s life.
Seeker has continued looking for Wanderer on her own, but Jeb captures her. Wanderer offers to show Doc the proper method of removing Souls, on the condition that he later remove her from Melanie’s body. Doc uses the technique to remove Seeker from her host, with both host and Soul surviving. Wanderer takes Seeker’s tiny alien form to a Soul space-travel site, where she sends it so far from Earth that it can not return for numerous generations.
Tired of the many lives she’s lived and finding it too painful to leave everyone behind, Wanderer makes Doc promise to let her die when she is removed and not tell anyone. The others in the shelter intervene with Doc, who inserts Wanderer into Pet, a human who was left brain-dead after the Soul inside her was removed. Now with a body of her own, Wanderer is able to be with Ian, while Melanie reunites with Jared.
A few months later, while on a supply run, Wanderer, Melanie, Ian and Jared are captured. They discover that their captors are humans, who reveal that there are several other human groups as well. They also learn that a Soul with this group has sided with the human resistance, as Wanderer has, and they may not be the last Souls to do so.