Thomas, portrayed by Dylan O'Brien, along with Newt, played by Thomas Brodie-Sangster, and Frypan, brought to life by Dexter Darden, are among the last survivors of the "Gladers" who are immune to the devastating Flare virus that has wreaked havoc on humanity. As members of The Right Arm resistance, they embark on a daring rescue mission to free other Immunes from a train operated by WCKD, the sinister organization responsible for capturing and experimenting on immune children. To their dismay, they learn that Minho, their missing friend and fellow Glader, portrayed by Ki Hong Lee, is not among the rescued, and is instead being held captive in "The Last City," WCKD's stronghold.
Defying the orders of Vince, the leader of The Right Arm played by Barry Pepper, the trio sets out on a perilous journey to save Minho, who is subjected to brutal torture in WCKD's efforts to find a cure for the virus. As they navigate the treacherous path towards The Last City, they are ambushed by Cranks—humans infected with the Flare—but are fortuitously rescued by Jorge, acted by Giancarlo Esposito, and Brenda, brought to life by Rosa Salazar.
Upon reaching the formidable wall encircling The Last City, they encounter a crowd clamoring for entry, only to witness WCKD's ruthless response when they open fire on the protesters. Soon, they are captured by a group of masked men, one of whom is revealed to be Gally, played by Will Poulter, who surprisingly survived the events of Minho’s attack at the conclusion of The Maze Runner. Gally then introduces them to Lawrence, played by Walton Goggins, a resistance leader who, while infected with the virus, possesses a scarce supply of an older antidote that barely sustains his life. He aids Thomas and Newt in entering the city covertly, where they soon encounter Teresa, portrayed by Kaya Scodelario. Gally believes she can help them infiltrate WCKD headquarters.
As tensions rise, Newt confides in Thomas about his own infection, prompting a promise from Thomas to find a cure. Inside WCKD's fortified compound, Teresa attempts to use Minho's blood to cure a Flare victim but ultimately fails. Unbeknownst to them, Ava Paige, played by Patricia Clarkson, and Janson, characterized by Aidan Gillen, reveal that the virus has now spread through the air within the city's walls, further complicating their mission.
Determined, Thomas, Newt, and Gally navigate WCKD headquarters. Gally takes charge of looking after the Immune children while Thomas, Newt, and Teresa search for Minho. Their plans are interrupted when they are discovered by Janson. In a desperate attempt to help, Teresa escapes to perform a crucial blood test on Thomas, whose blood holds the key to potentially curing the Flare.
After a series of dramatic encounters, including Gally's return to WCKD, the group eventually reunites with Minho and discovers that Thomas's blood can indeed save Newt. However, tensions peak when Newt, overwhelmed by the Flare's effects, implores Thomas to end his suffering. Faced with a heart-wrenching decision, Thomas is unable to follow through, leading Newt to take matters into his own hands.
In a gripping climax, Thomas returns to confront the ruthless Ava, only to witness her demise at the hands of Janson, who, infected and driven by desperation, ultimately captures Thomas. With Teresa at his side, they battle to escape and reclaim Thomas’s blood. The stakes elevate as they rush to the rooftop, where Teresa provides Thomas a vial of the sought-after cure right before tragedy strikes and she is lost during the collapse of WCKD's headquarters.
In the aftermath, the group successfully reunites with the Immunes and The Right Arm team, escaping to a sanctuary where the remaining population can find safety. As he grapples with the loss of his friends, Thomas discovers a note hidden in the pendant that Newt had given him—a final message urging him to watch over everyone. The journey concludes with Thomas facing the weight of their sacrifices and the hope for a brighter future.
