An earthquake occurs in Santorini, Greece, disrupting a wedding party. The shockwaves disturbs the Luna Temple which had been hidden in the sea for centuries. Lara Croft and the Petraki family decide to explore the ruins and find an Orb and a medallion among the treasures. Crime lord Chen Lo and his men however had followed them, and they kill the Petraki brothers and steal the artefacts. Lara manages to escape as a second earthquake occurs.
Back at Croft Manor, Lara is angry about the loss of the Petraki family. MI6 approach her for help to stop Jonathan Reiss from getting the orb and Lara realises that he is after Pandora's Box. She asks for help from Terry Sheridan, a traitor to the British Army.
After retrieving Terry from a Kazakhstan prison, he gets them into China to find the Shay-Ling. After a confrontation with Chen Lo, Lara learns of the whereabouts of the orb and Reiss, and retrieves the medallion back from him. Terry and Lara make a hasty escape, abseiling down the side of the mountain front head first before travelling to Shanghai.
They watch on as Reiss and Xien Lo try to exchange the Orb but Lara breaks it up. Reiss is able to get the Orb but Lara pole vaults towards the helicopter and places a tracking device on the box.
Lara and Terry follow the signal from the tracker to a shopping centre in Hong Kong. Reiss' laboratory is underneath the building so they break in when Reiss leaves. The orb is being translated and is almost complete. Lara records the spinning orb for Bryce to translate later on but Reiss and one of his mercenaries, Sean, return. Lara learns of Reiss' plans for Pandora's Box; to sell whatever is inside. After a gun fight, Terry and Lara escape with the orb, using Terry's escape plan. They head to the roof of the building and use the winged suits to fly out to sea.
Now on a ship, they rest. Lara and Terry kiss but Lara handcuffs him to the bed because she doesn't trust him and knows that she will end up killing him. From here, she heads to a barge and uses the family's television and Ariel to get in contact with Bryce. Little does she know that Reiss has broken into Croft Manor in the meantime and is holding Bryce and Hillary hostage. Bryce tries to stall in the translating of the sound that is needed to activate the orb but Lara is persistent and works out the problem. The Orb is activated and shows her the location of the Cradle of Life. She tells Bryce that it is in Kilimanjaro, Africa and she ends the call to head off. Reiss is now hot on her tail.
In Africa, Lara meets up with her old friend Kosa and he takes her to meet the tribesmen that live on the mountain. He translates for her and they tell her that it is dangerous and she should leave. People who go there never come back, but Lara is persistent once again and tells them that men are coming to get Pandora's Box. She has to get there to stop them from taking it. They allow her access and a few of the tribesmen lead the way.
They are stopped by Reiss and his men. All the tribesmen are killed. Reiss brings out Bryce and Hillary and uses them to persuade Lara and Kosa to lead him to Pandora's Box.
They head into the Petrified Forest, home to the Shadow Guardians who kill anything that move. Reiss's men are whittled down and Lara takes a chance and charges towards the plinth that takes the Orb. The ground opens up and she and Reiss fall in.
Meanwhile. Terry has gotten free and had asked the Chinese family on the barge of Lara's whereabouts. He is able to get to Kilimanjaro and frees Bryce and Hillary from their guards. They steal the helicopter and Bryce flies them over Petrified Forest.
After wandering around a maze-like cavern, they find Pandora's Box floating in a pool of acid. Reiss tries to get Lara to grab it but she runs off. He follows. Terry gets to the box and pulls it out with his rifle. He sees Lara and Reiss fighting up above so he distracts Reiss. Lara pulls him off the ledge; she is able to grab the ledge but Reiss falls into the acid pool and dissolves. Lara is pleased to see Terry but not amused that he is still planning on taking and selling the box. He slaps her, showing that he is not afraid to betray her and she shoots him. She looks towards the box and is tempted to open it but decides not to. She pushes it back into the acid pool.
She climbs out of the cavern and is greeted by Kosa and the tribesmen. The sun has risen so the box is still safe. She and Kosa rescue Bryce and Hillary from their unexpected wedding preps and the four of them drive off into the sunrise.