Wilson, 43, is in talks to play NFL commissioner Roger Goodell in the movie, which also stars Alec Baldwin, Albert Brooks, Gugu Mbatha Raw and Paul Reiser, reported The Wrap.
David Morse and Arliss Howard are also said to be nearing deals to join the Ridley Scott-produced movie which will see Peter Landesman in the directors chair.
Based on Jeanne Marie Laskas' GQ article 'Game Brain', the drama tells the story of Dr Bennet Omalu (Smith), a forensic neuropathologist who was the first to discover chronic traumatic encephalopathy (CTE) in NFL football players.
Smith will soon be seen in 'Focus', alongside 'The Wolf of Wall Street' star, Margot Robbie.
'Focus' will arrive to theatres on February 27, 2015 in the US and UK.