Unstoppable 2 takes place a decade after the original events. Frank Barnes (Denzel Washington) has retired, while Will Colson (Chris Pine) has become a senior railroad engineer.

The introduction of a new AI-controlled rail system promises to revolutionize rail safety. However, a corrupt cyberterrorist hacks into the system, sending a massive freight train filled with dangerous chemicals bound for a major city.

Frank is called out of retirement by Connie Hooper (Rosario Dawson) when Will and a rookie engineer find themselves aboard the runaway train without manual control. Racing against time, Frank guides them remotely as he uncovers a shocking conspiracy: the attack was an inside job, orchestrated by corrupt executives trying to profit from humanitarian aid contracts.

In a thrilling finale, Will and the rookie derail the train just outside town, saving thousands of lives. The film ends with Frank departing, leaving a legacy as the man who stopped two unstoppable trains.