While Unstoppable may come across as your typical action-thriller, this story didn't initially originate in the mind of a Hollywood screenwriter. It's actually based on a true story, granted in the loosest sense of the word. It even says "Inspired by true events" on the film's poster, so what's the real story?
A catastrophe could've very well happened in Ohio on May 15, 2001 when CSX Locomotive #8888 left its rail yard without anyone onboard to maneuver it (via Live About). It proved to be a simple error when an engineer forgot to turn off the engine to the vehicle and didn't activate the brakes. A train on the loose is bad enough on its own, but this vehicle also happened to have a significant amount of molten phenol (a toxic substance that's incredibly dangerous when inhaled, ingested, or touched) in a couple of the cars that could've resulted in substantial health problems had it been released in the surrounding area.
The movie took some liberties with certain details of the events, which is why it's "inspired" from a true story instead of "based" on one. For example, the runaway train in the film makes national headlines while it's still en route while in reality, the situation was handled before news stations around the country could air footage. Additionally, the train in the film reaches max speeds of 80 miles per hour whereas it only got up to about 50 mph in real life, but hey, that's Hollywood for you.
Since it's at least partly based on a true story, there probably wasn't a way to organically create a sequel. After all, it would've been pretty convoluted to have Washington and Pine's characters have to deal with another train situation going off the rails. It's more of a one-and-done-type story.
However, even if the studio wanted a follow-up to Unstoppable, there's another more tragic reason why a sequel will likely never happen.
