Following the disappearance of her father, Richard Croft, Lara Croft makes a living as a bike courier. When she is arrested after a bike accident involving a police car, Richard’s business partner Ana Miller posts her bail and warns her that if she does not claim her inheritance, her father’s estate will be sold off. Lara reluctantly accepts and gains access to a secret chamber in her father’s tomb. There she finds a pre-recorded video message from Richard detailing his research into Himiko, the mythical Queen of Yamatai who was said to command the power over life and death. Richard warns Lara to destroy all of his research but Lara decides not to so she can investigate further.
Lara travels to Hong Kong where she hires Lu Ren, captain of the ship Endurance, to sail into the Devil’s Sea and the island of Yamatai. The ship capsizes in a violent storm and Lara is washed ashore where she is knocked unconscious. She is revived by Mathias Vogel, the leader of an expedition to locate Himiko’s tomb. The expedition has been funded by a shadowy organization called Trinity that seeks to harness and weaponize Himiko’s power. Vogel takes Lara prisoner, claiming that he killed her father and intends to use Richard’s research to continue his expedition. He adds Lara and Lu Ren to his slave force but soon Lara escapes with the help of Lu, who stays behind after being severely injured.
Lara regains consciousness after nightfall and is forced to kill a Trinity guard when she is nearly discovered. She follows a mysterious figure wandering the island and discovers that the figure is her father, who stayed on the island to prevent Trinity from finding Himiko’s tomb. After Lara convinces him that she is real and not a figment of his imagination, Richard treats her injuries. Despite his protests, Lara sets off to recover his research from Vogel’s camp. Lara makes contact with Lu Ren, and he, along with the fishermen, stage distractions that allow Lara to infiltrate the Trinity camp and recover her father’s research. In the ensuing chaos, Richard makes his way to Himiko’s tomb and is captured by Vogel, who persuades Lara to open the tomb.
The party navigates a series of booby traps and locates Himiko’s sarcophagus. Two Trinity soldiers attempt to remove her corpse but become infected by Himiko’s “power”, which is actually a disease so potent that mere physical contact triggers immediate bodily disintegration, and reduces those infected to an aggressive zombie-like state. Images around the tomb reveal that Himiko, who was apparently immune to the virus herself and was a carrier, came to the island voluntarily rather than being forced as the legends imply, sacrificing herself to contain the virus. Vogel concludes that he cannot remove Himiko’s body and instead settles for detaching a finger, which he seals in a pouch. In the confusion, Lara and Richard overpower the remaining soldiers, though Vogel escapes and Richard becomes infected. Knowing there is no cure, Richard proposes destroying Himiko’s tomb to prevent the disease from spreading across the world. Lara pursues Vogel as Richard sets off a bomb, killing himself and sealing the tomb. Lara confronts Vogel and the two fight. Lara force-feeds him Himiko’s severed finger and kicks him into a deep chasm as the infection takes over. She escapes the tomb as it collapses and meets back up with Lu Ren and the fishermen, and commandeers a Trinity helicopter to escape Yamatai.
Lara returns to London, where she formally accepts her inheritance and inadvertently discovers that Trinity’s front company, Patna, is actually a subsidiary of Croft Holdings. She proceeds to investigate Trinity further and begins to suspect that Ana Miller is one of their agents who manipulated her into accepting her inheritance in order to have Lara sign over control of Croft Holdings’ business operations to her when Richard Croft stopped cooperating with Trinity. Having witnessed Trinity’s ruthlessness firsthand, she prepares for her next adventure.