Eli Frieden, Malik Bruder, Tori Pritel, and Amber Laska, four clones who escaped from a secret experiment called Project Osiris, are hiding in dorm rooms at McNally Academy, a boarding school in Pueblo, Colorado. Project Osiris, conceived by scientist Felix Hammerstrom and internet billionaire Tamara Dunleavy, cloned 11 children from notorious criminal masterminds and raised them in Serenity, New Mexico, a fabricated "perfect community" where their "parents" were actually scientists. A fifth clone, Hector Amani, died during their escape when their truck crashed off a cliff. The only person the clones know in the outside world is Randy Hardaway, a non-clone former Serenity resident sent to McNally after getting too close to the truth.
Their refuge collapses when they learn that agents of the Surety, Project Osiris's paramilitary enforcers whom they call the "Purple People Eaters," have been spotted in Pueblo. Six agents arrive at McNally. Tori pulls the fire alarm, and the clones slip into the crowd of evacuating students. When agents give chase, Eli drops the campus flag onto five of them while Malik tackles the sixth. Amber commandeers the Surety's SUV, and Eli drives onto I-25 North into heavy traffic. At the Denver South Park-n-Ride, they abandon the vehicle and board a city bus, losing the pursuing helicopter.
In Denver, Eli discovers at an internet café that human cloning is illegal worldwide and they are the only human clones in existence. Amber sees this as proof that Project Osiris is a crime and impulsively reports it to a traffic officer, who dismisses her and has her taken to a precinct house. Tori poses as Amber's sister, learns Amber will be sent to a police psychologist at the Medical Arts Center, and the group stages a rescue, rappelling out a third-floor bathroom window on a fire hose and fleeing as the officer gives chase.
With police searching for them, they hide in a tree-service dump truck's load of branches. The truck drives to a municipal yard and begins feeding its cargo into a wood chipper. The four cling to the truck bed as branches slide toward the blades, saved only when the back flap closes. They break into a vacationing family's house in the Denver suburb of Mountain View, where a TV news report reveals that Amber's photograph has been broadcast. Tori disguises Amber by cutting and dyeing her hair. Eli proposes seeking Tamara Dunleavy, who co-founded Project Osiris but withdrew before the experiment began and now lives near Jackson Hole, Wyoming.
When a pop-up alert shows the homeowners' flight has landed, the clones flee in the family's Jeep. To prevent police from tracing the vehicle to the bus station, Malik leaves it running in a rough neighborhood. The group separates and boards a bus to Jackson Hole.
There, they canvass local businesses and trace Dunleavy to a charitable society meeting. When Dunleavy sees Eli, she startles, seeming to recognize someone else's face. Eli tells her they are Osiris clones and asks for help, but she denies everything and walks away. Afterward, Malik notices she kept staring below his left ear. Tori examines the spot and finds a small bump with a faint scar; all four clones have identical marks. Amber concludes these are implanted chips that generated the nausea the clones experienced near Serenity's borders. She fires a staple gun into her own neck as a pretext for an emergency room visit, where a doctor removes both the staple and a tiny electronic tracking chip. In a park, Amber extracts the remaining chips from the others using a box cutter and improvised supplies.
Returning to their picnic table, they catch Dunleavy's chauffeur rifling through their backpacks, where he has tucked $500 into each bag. Tori interprets this as guilt money from Dunleavy. The group takes Dunleavy's Bentley and flees, with Eli arguing that the only remaining evidence lies inside the Plastics Works, the factory in Serenity that housed Osiris's operations and records.
They drive through the Rockies, avoiding Denver. In Taos, New Mexico, they steal a Splash! Pool Maintenance truck, a vehicle familiar in Serenity, and hot-wire it. On the road into Serenity, they pass the broken railing where their escape truck crashed. None of them feel sick, confirming the chip removal worked. Serenity is deserted. Inside the Plastics Works, the conference room has been torched: filing cabinets melted, records reduced to ash. In a rage, Malik kicks a broken vase, revealing a single sheet of paper preserved beneath it by the vase's water. They freeze the damp page to stop the ink from degrading further, then decipher it under a magnifying lamp. It contains 11 names, seven legible, matching the number of clones.
Using the factory's unrestricted internet, they identify the seven readable names as notorious criminals and match them to specific clones. Gus Alabaster, a Chicago mob boss, matches Malik. Mickey Seven, a radical activist turned terrorist, matches Amber. Yvonne-Marie Delacroix, a brilliant bank robber, matches Tori. C. J. Rackoff, a swindler, matches Hector. With all other males accounted for, Eli concludes he is almost certainly cloned from Bartholomew Glen, the Crossword Killer. Tori proposes visiting Rackoff at Kefauver Federal Detention Facility near Haddonfield, Texas, reasoning he might provide testimony and DNA evidence.
They repaint the truck with a fake logo and alter the license plates for the drive to Texas. At the Tumbleweed Inn near the prison, they are stunned to discover Hector alive. He survived the crash, returned to deserted Serenity, and independently traced Rackoff through a parent's diary. At the prison, the elderly Rackoff recognizes Hector as his clone and confirms he knew about Osiris but refuses to cooperate unless they break him out.
Tori devises an elaborate plan. Rackoff fakes an allergic reaction during a supervised picnic to reach the second-floor hospital, then slides down a laundry chute to the basement workshop and hides among shrink-wrapped mailbags. Meanwhile, the clones ambush the postal worker who collects mailbags daily. Malik, wearing the worker's uniform, drives the postal van into the prison and out again with Rackoff concealed in the shipment.
The triumph is short-lived. A military helicopter lands ahead of the van and SUVs close in from behind. Rackoff reveals the truth: Hector, believing himself abandoned after the crash, returned to Serenity and struck a deal with Osiris to lead them to the other clones in exchange for his safety. The prison break was orchestrated by Osiris all along. Hector tearfully confirms the betrayal.
The four original clones use a heavy shipping skid as a battering ram to crash out of the van. Malik and Amber ride the skid down a steep embankment into a rushing river and are swept downstream. Eli finds a dropped tranquilizer syringe, sedates Hammerstrom, frees Tori, and commandeers the unguarded helicopter by threatening the pilot. From the air, they briefly glimpse Malik and Amber clinging to the skid in white water before losing sight of them. The helicopter runs out of fuel near Lubbock, Texas. The story ends with the group split in two: Eli and Tori fleeing on foot toward Lubbock, uncertain whether Malik and Amber survived. Eli reflects that the skills encoded in their DNA, however unwanted, have carried them this far, and resolves that as masterminds, they can still find a way to bring down Project Osiris.