The film begins on Santorini Island, Greece, during a wedding when it is interrupted by an earthquake. The earthquake uncovers the Luna Temple, built by Alexander the Great to house his most prized treasures. The Luna temple was swallowed by the sea during a volcanic eruption in 330 BC and by law no-one was allowed to record its exact location. Lara finds the location of the temple by studying the changes in ocean currents along the oceanic shelves after the Earthquake.Among these treasures is a glowing orb with a pattern resembling a code etched into it. Inside the temple, Lara also finds references to Pandora's Box. Lara finds this orb; but it is stolen by the crime lord Chen Lo (Simon Yam), who had followed Lara into the temple. Lara has to retreat as the entire temple collapses and sea water rushes in.MI6 inform Lara that the Orb was stolen from her by Chen Lo to deliver to Reiss, but they don't know why. MI6 say that Chen Lo and his gang the Shay-Ling is working for Reiss. Jonathan Reiss (Ciaran Hinds) is Nobel Prize-winning scientist turned bio-terrorist who has been behind every act of bio-terror in the last 15 years.Lara tells MI6 that she saw references to Pandora's Box inside the temple. Legend has it that an Egyptian Pharoah found the Cradle of Life in 2300 BC. This was the place where life began. There he found a box, the box which brought life to Earth. When he opened the box all that was left inside was anti-life or Ramante. Life is about balance, so the box came with life and anti-life. The Ramante leveled the Pharaoh's army. Pharaoh tasked his finest warrior to transport the box to the end of the world. 2000 years later, Alexander reached India where his army was ravaged by a plague after one of men found a box among some remains. Alexander returned the box to the Cradle of Life. The key to finding the box, which is hidden in the mysterious Cradle of Life, is a magical luminous sphere that serves as a map, the one stolen by Chen Lo in Santorini (Simon Yam), who plans to sell the sphere to Reiss.Lara (Angelina Jolie) is tasked by MI6 to find Pandora's Box, an object from ancient legends that supposedly contains a deadly plague. Reiss is in the business of creating bio-weapons and selling them to the highest bidder. Reiss had contracted Chen to acquire the Orb for him and demands $100 million each from his business partners in exchange for access to the bio-weapon coming out of Pandora's Box. Sean (Til Schweiger) is Reiss's head of security.Lara analyzes the footage from the temple with Hillary, her technology guy. To help her track down Chen Lo and the ball, Lara recruits an old lover, Terry Sheridan (Gerard Butler), a former mercenary and Royal Marine, who was in prison in the Republic of Kazakhstan. Terry worked for the Shay-Ling and knows everything about their methods and their hideouts. Lara offers an expunged record, 5 million pounds and a new life to Terry in exchange for his help.Lara and Terry's enter into China. Terry takes Lara to the Shay-Ling HQ in the mountains. Meanwhile, Chen is holding on to the Orb to get more money out of Reiss. Reiss promises $12 million if Chen can also deliver Lara's body. At the Shay-Ling HQ, Chen tries to kill Lara, but she beats Chen and finds that the Orb will arrive at the Flower Pagoda in Shanghai at a designated time for handover to Reiss. She takes a medallion from Chen which he had taken from her inside the Luna temple. Looking at the inscriptions on the medallion, Hillary figures that the Orb will be unlocked by sound.Lara and Terry fight in suburban Shanghai but Reiss manages to take the Orb with him in a helicopter. Lara puts a tracking device on the Orb crater and tracks it to Hong Kong. Lara and Terry steal the Org from Reiss's lab (where Reiss tells her that he will use the buyers to release the virus but make money by selling the only antidote in the world) and leap off the then-under-construction International Finance Centre skyscraper in Hong Kong, landing on a ship out in the Kowloon Bay after taking the Orb from Reiss.The Orb later reveals the location of the Cradle of Life to be somewhere near Mount Kilimanjaro in Tanzania. Lara sends this information to Bryce (Noah Taylor) back at Croft Manor. After the transmission, it is revealed that Reiss and his men had infiltrated the mansion and captured Bryce and Hillary (Chris Barrie). Meanwhile, Lara and Terry begin to fall in love again; but Lara starts to back away from him. She seduces him one morning, then leaves him handcuffed to a bedpost as she believes that at the lab Terry had the chance to kill Reiss and he did not take the shot.Lara meets up with Kosa (Djimon Hounsou), an African friend who serves as her translator as they obtain information from a local tribe about the Cradle of Life. Kosa translates for the tribe's Chief, stating that the Cradle of Life is in a crater protected by the "Shadow Guardians". As the expedition sets out, Lara, Kosa, and the tribesmen with them are ambushed by Reiss' soldiers. Many of the tribesmen are killed by Reiss' soldiers with some of the soldiers being killed by Lara in the fight. The fight ends with Lara surrendering to overwhelming odds as Reiss' helicopter starts to land. Reiss and Sean (Til Schweiger) threaten to kill Bryce, Hillary, and Kosa unless Lara leads him and his men to the Cradle of Life.Upon arrival at the crater, they encounter the Shadow Guardians which kill immediately when they sense a movement. Sean and most of Reiss' soldiers are killed by the creature. When Lara drops the Orb into the hole that opens the entrance to the Cradle of Life, the Guardians disappear. Inside the Cradle of Life, there is a pool of highly corrosive black acid, which holds the box and where the laws of physics do not apply, as Lara and Reiss are able to walk (upside down) along the ceiling of the cave. Terry arrives, frees Reiss' captives, and catches up to Lara.Following a climactic fistfight between Lara and Reiss, Reiss is knocked into the acid pool by Lara after he is distracted by Terry. When the couple tries to leave, Terry attempts to take the box as compensation for finding it; but she staunchly refuses to let him. Despite her love for him, this results in Lara being forced to fatally shoot him in the stomach in self-defense just after Terry draws his own gun preparing to shoot Lara. Lara places Pandora's Box back into the pool, and is tempted to open the box herself, but realizes that some boxes are not meant to be found.