Ryan, 52, is set to make her directorial debut with Ithaca, which is an adaptation of William Saroyan's classic 1940s novel The Human Comedy. According to The Hollywood Reporter, Hanks, 57, is in negotiations to appear in the film alongside Ryan.
Set during World War II, Ithaca tells the story of a teenage boy in a small California town, who is left to care for his family after the death of his father and the departure of his older brother for the war.
Hanks has already signed on to executive produce the film with his Playtone company, and he is reportedly inching closer to agreeing to act in it, as well. Ryan is currently booked to star with Sam Shepard, Melanie Griffith and Jack Quaid, her son with ex Dennis Quaid.
Ithaca also marks Ryan's return to the big screen after a bit of a hiatus. While she has been making appearances in shows such as Web Therapy and Curb Your Enthusiasm, her last film credit was for 2009's Serious Moonlight.
Hanks and Ryan famously starred in three films together in the 1990s: 1990's Joe Versus the Volcano, 1993's Sleepless in Seattle, and 1998's You've Got Mail. They have remained friendly over the years and reunited in April 2013 for the opening of Hanks' Broadway show Lucky Guy.