The 57-year-old actor and 52-year-old actress previously collaborated on Joe Versus the Volcano (1990), Sleepless in Seattle (1993) and You've Got Mail (1998). Ithaca marks Ryan's directorial debut, and Hanks will serve as producer on the film.
The feature is set during World War II, and is based on William Saroyan's 1942 novel The Human Comedy. The book makes several references to Homer's epic poem Odyssey, and the two main characters are named Homer and Ulysses. The pair are brothers who live with their siblings and single mother (Ryan) in Ithaca, Calif.
Casting is currently underway, and the movie will be filmed in central Virginia.
"We're happily surprised by the cinemagraphic opportunities, the talent of the filmmaking community and the variety of resources at our disposal," Ryan lauded of the state. "We couldn't be more delighted to be here."
"We couldn't be happier that Megan Ryan has chosen Virginia as the location for her directorial debut," Virginia Governor Terry McAuliffe said. "We are excited to have the opportunity to work with Meg Ryan and Tom Hanks on this film about an important time in American history."
Hanks will reprise his role as Robert Langdon in an upcoming adaptation of Dan Brown's The Lost Symbol, while Ryan is rumored to be the voice of the narrator on upcoming How I Met Your Mother spinoff How I Met Your Dad.