The film begins with a pregnant woman waiting for a bus in the dead of night. Shortly after she boards bus #657, the vehicle is hijacked by thieves. The story unfolds one week earlier, where Detective Dog (or Derrick), played by Morris Chestnut, and Mr. Pope, portrayed by Robert De Niro, interrogate a couple regarding a missing fortune. When the man eventually provides an answer, Dog responds with lethal force, killing them both.
Meanwhile, Luke Vaughn, a casino employee played by Jeffrey Dean Morgan, struggles as he visits his sick daughter in the hospital. The meager earnings from his job can't cover her medical bills, and he pledges to the doctor he will have the funds for her operation by Friday, or face devastating consequences. Back at the casino, desperation drives Vaughn to plot a robbery with the help of his co-worker Cox, who is portrayed by Dave Bautista. Cox shares insights about the casino's lucrative lifestyle, which further ignites Vaughn's plan.
In a fateful meeting with Pope, Vaughn pleads for at least $300,000 to save his daughter, but is met with refusal and promptly fired. In a twist of fate, Vaughn, Cox, and an unnamed accomplice decide to execute the robbery that very night. Chaos ensues when an employee spots them, and as the situation escalates, a gun is drawn, killing the employee. They flee as a shootout erupts with Dog and his team, wounding one of the thieves. With their getaway car in disarray, they hijack bus 657, unaware that police, led by Officer Kris Bauhaus, played by Gina Carano, are hot on their trail, a few blocks behind the bus.
As the bus speeds away, Kris hears gunfire and gives chase, seeking to bring the situation under control. Vaughn and the others remove their masks, making their identities known to Dog and his crew. When Kris approaches, the atmosphere shifts; the thieves attempt to act composed. However, when Kris insists the bus pull over, chaos erupts as Cox fires a shotgun in her direction, narrowly missing her. The police set up roadblocks, and Vaughn, seeking negotiation, inscribes the passenger's phone numbers on the bus window. He demands that Kris clear the roadblocks, threatening the hostages, including the boy and the pregnant woman, Pauline.
Kris complies, and they make their way onto the interstate. As dawn breaks, tensions rise—one wounded thief is dying, prompting Vaughn to call on a student passenger with veterinary skills for help. While Cox communicates with Jono, a contact assisting their escape, another male passenger attempts to take control but is swiftly subdued by Vaughn.
Realizing their fuel is running low for a trip to Galveston, Texas, they call for a fuel tanker, prompting a tense side plot where Kris drives to facilitate the refueling process under the watchful eye of Detective Marconi, who supports Kris. During the refuel, Vaughn makes a pivotal decision to release two hostages, recognizing how much he wants to see his daughter survive. Meanwhile, the wounded thief succumbs to injuries, creating more chaos in the bus as others struggle for survival. As the tension mounts, one of the remaining passengers, now emboldened, attacks Marconi, leading to a fierce confrontation.
With SWAT teams surrounding the bus and mounting pressure, Cox takes drastic measures, threatening lives to assert control. A sudden turn of events sees Cox shot down by Vaughn, who ultimately reveals his cunning plan. Just as Vaughn receives emotional news from his daughter about the hospital, he later orchestrates a clever escape, releasing hostages and vanishing into the night under cover.
As Vaughn plots vengeance against Jono, who has a tragic fate waiting for him, he finds himself ensnared by Dog and Pope. A tension-filled standoff reveals a shocking twist about Pauline, uncovering secrets about her true nature and her link to Vaughn’s plans. The film crescendos in chaos, with dogged determination from both sides as Vaughn stakes everything for his daughter’s future, culminating in an explosive finale that reveals the true stakes of desperation and survival.
