Trapped in their New York brownstone's panic room, a hidden chamber built as a sanctuary in the event of break-ins, newly divorced Meg Altman and her young daughter Sarah play a deadly game of cat-and-mouse with three intruders - Burnham, Raoul and Junior - during a brutal home invasion. But the room itself is the focal point because what the intruders really want is inside it.

When a scientist discovers the possibility of the meaning of life, two shadowy organizations learn of this and will stop at nothing to steal the scientist's work for themselves. As a result, two burned-out assassins named Puritan and Sultan are assigned to protect the scientist and keep his project from falling into the wrong hands.