- A sick and desperate John travels to Mexico for a risky and experimental medical procedure in hopes of a miracle cure for his cancer only to discover the entire operation is a scam to defraud the most vulnerable.
- John Kramer (Tobin Bell) is back. The most chilling installment of the SAW franchise yet explores the untold chapter of Jigsaw's most personal game. Set between the events of SAW I and II, a sick and desperate John travels to Mexico for a risky and experimental medical procedure in hopes of a miracle cure for his cancer - only to discover the entire operation is a scam to defraud the most vulnerable. Armed with a newfound purpose, John returns to his work, turning the tables on the con artists in his signature visceral way through a series of ingenious and terrifying traps.—Lionsgate
- The movie opens with John Kramer (Tobin Bell) undergoing an MRI scan in a hospital, being told afterwards by a doctor that due to his advanced brain cancer, he has only months left to live. While John is at the hospital, he notices a custodian (Isan Beomhyun Lee) attempting to steal a patient's belongings. The custodian later wakes up in a trap set up by John, his hand caught in a mechanical contraption and two vacuum tubes hooked up to his eyes. He has 60 seconds to turn a dial that will activate the contraption, breaking all five fingers on his right hand one by one, or else his eyes will be sucked out by the vacuum tubes. He only manages to break three of his fingers before the timer runs out and he gets his eyes vacuumed out, however, the trap sequence is revealed to have taken place entirely in John's imagination, and the custodian puts back the patient's belongings after noticing John watching him.
At a support group meeting for cancer patients, John comes across Henry Kessler (Michael Beach), who claims to have terminal cancer and vows to keep fighting it until the end. Four months pass, and a bereft John is sitting in a coffee shop, about to sign his last will and testament, when he encounters a seemingly much healthier Henry, who claims to have been cured by an experimental cancer treatment given by Norwegian doctor Dr. Finn Pederson (Donagh Gordon). After doing some research, John finds the website of Pederson's daughter, Dr. Cecilia Pederson (Synnøve Macody Lund), who is continuing her father's work and claims that corrupt pharmaceutical companies have been going after him, thus forcing her to perform further clinical trials of the treatment off the grid. John gets in touch with Cecilia, who refers him to her makeshift clinic in Mexico City for a surgery in two weeks' time.
John travels to Mexico City and, upon arriving, is given a tour of the city by taxi driver Diego (Joshua Okamoto), who takes him to the facility, located in a remote location just outside the city boundaries. He is introduced to Gabriela (Renata Vaca), who claims to have been cured by Cecilia's treatment, as well as Cecilia and the rest of her medical team: nurse Valentina (Paulette Hernandez), anesthesiologist Mateo (Octavio Hinojosa) and surgeon Dr. Cortez. As Cecilia takes John to the operating room, located within an abandoned chemical factory, he encounters a young boy, Carlos (Jorge Briseño), playing with a soccer ball outside the facility. Before his surgery, John speaks with Parker Sears (Steven Brand), who has just undergone a similar operation. Cecilia and her team conduct the surgery on John, and he awakens to find Cecilia congratulating him and assuring him that the surgery was successful. Believing himself to be cured of his cancer and finding a new lease on life, John purchases a bottle of tequila as a gift for Gabriela. Upon returning to the facility to present the gift, John finds the operating theatre abandoned and in a state of disarray. John realizes that the surgery never actually took place, his brain tumor was never removed and the experimental treatment was an elaborate scam.
After figuring out that "Dr. Cortez" was Diego in disguise, John abducts the taxi driver. Diego wakes up back in the facility with John watching over him as his test begins. Diego has two pipe bombs wired into his arms and he must use two scalpels attached to his hands to cut through his flesh in order to remove the explosives. Diego survives his test and gives up information about the rest of the con artists. Meanwhile, while closing up his veterinarian's office, Mateo sells drugs to a desperate Gabriela, before he is abducted moments afterward by an assailant in a pig mask. The same assailant kidnaps Valentina while she is being assaulted by a stranger in his car, before going on to kidnap Gabriela from a nightclub bathroom and Cecilia from her home as she tries to escape in her car. The kidnapper removes their mask moments before Cecilia is abducted, revealing themselves to be Amanda Young (Shawnee Smith), John's apprentice, with both her and John working together to kidnap Cecilia.
Valentina, Cecilia, Mateo and Gabriela all wake up back in the disused factory they had used as the facility for their fraudulent activities, finding themselves in a deadly game overseen by John and Amanda. Valentina is the first to be tested, tasked with amputating her own leg with a Gigli saw and extracting an amount of bone marrow from her body. While she succeeds in cutting off her leg, she fails to extract the bone marrow in time and is subsequently decapitated by a wire. Cecilia's phone, located on a trolley, starts ringing, but is out of reach from everyone. Cecilia then disembowels Valentina's corpse and uses her intestines as a rope to pull the trolley close enough to reach her phone, making a call to someone and revealing she's been kidnapped but being interrupted when Amanda gives her an electric shock. Amanda, having struggled with drug addict herself in the past, expresses apprehensive over the prospect of Gabriela being tested. Mateo is the next to be tested, being tasked with cutting into his own skull and removing a piece of his own cerebral tissue and place it into a container of enzyme fluid in order to deactivate his trap. He removes a piece of brain matter successfully, however, it is not dissolved by the enzyme in time to release him, resulting in his death when a mask closes around his face and burns it.
During the games, Parker returns to the compound, armed with a gun and demanding his money back after realizing the operation was a scam. As he navigates through the building, he is found by John and Amanda and is then chained up to a chair and made to watch the tests unfold. Gabriela is suspended in the air from shackles around her wrist and her ankle and put before an X-ray machine that will burn her flesh. To free herself, Gabriela must use a sledgehammer to break her wrist and ankle. She does so, and falls to the ground, heavily injured but still alive. John orders Amanda to take Gabriela to the hospital, but before she can, Parker holds the two of them at gunpoint and demands them to free Cecilia. As they unchain Cecilia, she shares a kiss with Parker before revealing that he was in on the scam from the beginning and that he was the one she had called on her phone, killing Gabriela by snapping her neck, which leaves Amanda distraught. Cecilia and Parker force John into one of his own traps at gunpoint, chaining him up in the same place Cecilia was in. Before she can do the same with Amanda, she hears Carlos playing with a soccer ball outside the facility again and takes him inside, chaining him up opposite John and wanting John to witness someone completely innocent meet their death in one of his traps, all while John pleads with them to stop what they're doing. The trap activates itself, revealing itself to be a seesaw-like contraption that begins to waterboard the two of them with blood. The two of them can pull levers to tilt the seesaw in their direction and thus bear the full brunt of the blasts, and John forces himself to endure non-stop blood-boarding in order to ensure Carlos' safety. Parker and Cecilia run to the room in which Amanda and John were controlling the games earlier in order to run away with the bags of money they'd acquired from the scam, however, upon taking the bag of money, it actives a tripwire that stops the blood-boarding trap. As Amanda frees Carlos and John, John watches from below as Parker and Cecilia find themselves trapped inside the control room in a test of their own, which is now filling up with a toxic gas. Their only respite is a hole in the wall that will only fit one of their heads, with Cecilia stabbing Parker to death in order to fit her head through the hole and escape the effects of the gas. The timer runs out and the gas stops coming out, but Cecilia is left trapped in the room as John, Carlos and Amanda exit the building, the movie ending as they walk out into the sunset together.
In a mid-credits scene, John and another apprentice of his, Detective Mark Hoffman (Costas Mandylor), are overseeing Henry in a disused industrial bathroom (as seen in "Saw"), placing him in a trap intended to disembowel him.
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