NOTE: This spoiler was submitted by Jeremy

The film opens with Nathan Drake (Tom Holland) hanging outside a plane, tangled up in fallen cargo. He attempts to climb back up inside, dodging henchmen and more falling cargo. Just as he makes it back to the top, he gets hit by a car falling out of the ramp. As Nate falls, a hand reaches out to grab him.

Cut to a flashback, 15 years earlier in Boston. Nate (here played by Tiernan Jones) and his older brother Sam (Rudy Pankow) are breaking into a museum to steal the original map of Ferdinand Magellan’s expedition, as the legend states that Magellan’s whole voyage was to find hidden gold. The brothers are caught by security, and because this is Sam’s third strike, the orphanage that houses both boys is kicking Sam out and forcing him to stay elsewhere, away from Nate. Nate goes to their room and catches Sam sneaking out to be on his own, but he promises his little brother that he will return for him. Sam leaves him with a ring belonging to their ancestor Francis Drake, with the inscription “Sic Parvis Magna” (“Greatness from small beginnings”).

Present Day – Nate works as a bartender. He serves a snooty rich girl and uses an opportunity to swipe her bracelet when she’s not noticing. Nate is observed by a fortune hunter named Victor “Sully” Sullivan (Mark Wahlberg). He offers Nate a chance to work together, but Nate declines. He soon finds that Sully swiped the bracelet from him and left him his business card.

Nate goes to Sully’s office to get the bracelet back but then comes across other artifacts in Sully’s possession, including the same map that he and Sam were trying to take. Sully reveals he used to work with Sam and knew that Nate was his brother. They discuss Magellan’s voyage and how it was bankrolled by the Moncada family, responsible for various atrocities throughout history. Sam had helped Sully steal the diary of Juan Sebastian Elcano, with clues that can lead them to Magellan’s fortune. Nate is initially unwilling to help Sully finish any work that he and Sam started, but Nate looks over postcards that Sam had been sending him throughout the years, and he soon changes his mind and calls Sully.

Sully informs Nate that they must acquire a golden cross that is one of two keys needed to finding Magellan’s gold. He has the first one, and the second one is being held for auction at a museum. Sully knows that Santiago Moncada (Antonio Banderas) will try and buy the cross since he feels it is his birthright. The duo make preparations for their heist, with Nate doing some background checking on Sully to know who he’s working with.

The two go to the auction, where Sully is unsettled when he sees a woman named Jo Braddock (Tati Gabrielle) there. He knows her as a mercenary and has had run-ins with her in the past. Braddock approaches Sully, indicating she knows he’s there for the cross as well. Nate is set to go kill the power as the auction commences, but he is caught by Moncada’s big burly Scottish henchman (Steven Waddington). Sully has to buy time by attempting to outbid Moncada, despite knowing he doesn’t have the money for it. After evading the Scotsman and another thug, Nate eventually causes a diversion by dangling from the chandelier and creating a commotion. Sully grabs the cross and makes his exit, but is nearly intercepted by Braddock until other guards show up, and she deals with them violently. Nate escapes the other security guards and gets into Sully’s car to ride off together.

Nate and Sully take the cross and travel to Barcelona to meet with Sully’s associate, Chloe Frazer (Sophia Ali), who is in possession of the second cross. She doesn’t trust Nate being there with Sully, but she proves her own untrustworthiness moments later by swiping the cross out of Nate’s bag. Nate and Sully chase after Chloe, but although she nearly gets away, Nate reminds her that she doesn’t actually know where to find the treasure without their help. Based on clues that Nate had studied in the diary, he figures that they have to start by going to a church, Santa Maria del Pi. While they stay in a hotel room overnight, Chloe brings up something that Sully isn’t telling Nate about Sam.

At the Moncada Foundation Headquarters, Moncada is upset to learn that his father Armando (Manuel de Blas) is donating the family fortune. He tells Santiago that he is not worthy of inheriting it. After having one last chat with his father, Moncada has Braddock kill Armando before taking the money to set off on his own expedition.

Nate, Sully, and Chloe go to the church and find the secret passageway underground. Using the crosses, they try to open an entrance, but they accidentally set off a booby trap thanks to Sully misreading the instruction in the diary. Nate and Chloe go down the entrance with one key while leaving the other with Sully. Down there, Chloe says she mistrusts people because her own father took off with money from a discovery she made and abandoned his family. They end up in a nightclub with the next passageway hidden behind the bar. The Scotsman and another goon of Braddock’s find them, while Braddock herself is tailing Sully. Nate and Chloe manage to create a diversion and fight off the Scotsman before making their way through the entrance.

Nate and Chloe come across a trap door, using their cross to try and unlock it. The room then begins to fill up with water, with Sully needing to use the other cross to help get them out. He is ambushed by Braddock just as he finds the other keyhole is in the wall of a restaurant behind glass. Sully fights Braddock and throws her against the glass to break it open and help free Nate and Chloe before they drown. Once they are clear, the two find another room where both crosses are needed to unlock the door. Sully throws his cross down, and Nate and Chloe find giant urns where they think the gold is hidden. Instead, they are all filled with salt, and they each break. Nate finds a map hidden among the salt, indicating that the treasure is in the Philippines. Unfortunately, Chloe takes this opportunity to deceive Nate and take the map for herself. She tells Nate that Sully is keeping the truth about Sam from him before she pistol-whips him and knocks him out.

Sully finds Nate, but when he wakes up, he asks Sully what happened to Sam. Sully admits that he and Sam were ambushed by Braddock, who shot Sam, and Sully had no choice but to run and leave him behind, leading them to believe that Braddock killed Sam. Nate angrily walks away from Sully.

Braddock meets with Moncada, who reveals that he had hired Chloe as part of his team, and she brings him the map. He makes preparations to head to the Philippines with his crew. Nate and Sully reconcile and plan to stowaway on the plane by hiding in the trunk of Moncada’s car. In the plane, Moncada gathers his crew and talks about how he feels that Magellan’s crew betrayed his family, and that the gold they were supposed to find belonged to the Moncadas. Braddock then betrays Moncada and slits his throat in front of the crew, then takes charge of them. Nate and Sully sneak out, but Nate’s pride gets the best of him and he makes his presence known to confront Braddock about shooting Sam. He lets the cargo chutes open, leading Sully to fly out of the plane with his own chute, while the henchmen are thrown from the plane. Chloe gets in the car with the map that knocks Nate out, and the two manage to grab onto a cargo load with a parachute and land in the ocean. They float until they reach an island resort.

Nate and Chloe get a room and try to look over the map, but they find that it doesn’t pinpoint the treasure’s exact location. While Chloe sleeps, Nate uses one of Sam’s postcards and lights a flame under it to show a hidden message, saying “The keys are your compass.” Nate uses the crosses and finds the exact spot on the map. He writes down fake coordinates, knowing Chloe will see them and run off them them. She does, and Nate pulls out the right coordinates.

Nate uses a speedboat to head to the location, just as Braddock and her goons arrive as well. Sully finds Nate, who comes across the cavern with two intact ships. The gold also happens to be inside the ships. Just as Nate and Sully are helping themselves to the treasure, Braddock has the ships airlifted out of the caverns, since the ships themselves are worth billions. Sully climbs up to one of the choppers and knocks out Braddock’s goons. She notices him in the other chopper, and her men begin to attack. Nate and Sully fight the men on the ship, knocking them into the ocean. The Scotsman ends up crashing his chopper and one of the ships on the side of a giant rock. Braddock attempts to go after Nate and kill him herself. As Nate tries to climb to the chopper, Sully has to make a choice over saving him or the gold. Sully throws the bag of gold at Braddock, sending her falling into the ocean. He pulls Nate up, and the second ship drops right on top of Braddock, crushing her.

Nate and Sully start flying away, with Nate revealing he saved some gold. They look down and tauntingly wave at Chloe on her speedboat, knowing she has been tricked. The pair then fly off together on their next adventure.

Before the credits roll: We cut to a prison where we see that Sam is still alive and is writing another postcard to Nate.

Midway through the credits: Nate is meeting with a man named Gage (Pilou Absaek) over acquiring an item for a man named Roman (setting up the events of the first video game). Sully is also sporting a mustache, which Nate makes fun of. Just as the guys think they are making their escape, they are ambushed by gunmen.

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Nathan Drake has always been fascinated with history and hidden treasures thanks to his older brother Sam, who disappeared when they were kids. In the present day, Nate teams up with Victor "Sully" Sullivan, a former associate of Sam's who wants Nate's help in finding the hidden gold of Ferdinand Magellan. With help from Sully's other associate Chloe Frazer, the team explores through Barcelona using two crosses as keys to help find the gold, all while another treasure seeker, Santiago Moncada, and his mercenary partner Jo Braddock make their own plans to get the gold, since Moncada's family had funded Magellan's expedition and he feels betrayed out of their wealth.

Nate finds a map that leads to the treasure in the Philippines, but Chloe betrays him and takes the map since she was working for Moncada. Braddock then betrays and kills Moncada to take over his crew. Nate deduces the exact location of the treasure and gives Chloe fake coordinates since he knew she would trick him again. He and Sully find the treasure, but Braddock and her goons airlift Magellan's ships out of their hiding places, along with the treasure inside them. The first ship is destroyed, and Braddock's men are killed. Braddock fights Nate, but Sully sacrifices his gold to drop it onto Braddock to save Nate, sending her into the ocean and letting her get crushed by the second ship. Nate and Sully manage to recover some gold while Chloe ends up empty-handed.

Nate and Sully set off on their next big job, while it is revealed that Sam is still alive but in prison