Deadline reports that the duo are close to striking up a deal to board the $80 million (£50m) project, which is under the jurisdiction of Emmett/Furla Films, Scott Free and 20th Century Fox.
Lucky Strike, scripted by Henry Bean, follows a police officer who joins forces with an infamous drug runner to take down a cartel. Production is scheduled to commence in late summer or early autumn.
Scott's last directorial outing was Unstoppable, which starred Chris Pine and Rosario Dawson. He is currently working on Hell's Angels and a remake of Walter Hill's The Warriors.
Vaughn is expected to reteam with his Wedding Crashers co-star Owen Wilson for another 20th Century Fox venture, Interns. He will also appear alongside Ben Stiller in Neighbourhood Watch.
Lucky Strike is yet to be given a potential release window.
Watch a clip from Tony Scott's Unstoppable below: