The film, which is also Ryan's directorial debut, follows Colony star Alex Neustaedter as teenaged bicycle messenger Homer Macauley as he comes of age during the global conflict.
The trailer, released Wednesday, features Homer delivering messages to his small town regarding the war and how he keeps in touch with his older brother (Jack Quaid) who is stationed overseas.
Ryan and Hanks portray the parents of the brothers who live out on a small farm. The former romantic comedy powerhouses are seen nodding at each other as Ryan's character is working out in the field.
"Homer delivers messages of love, hope, pain and death to the good people of Ithaca, but soon must grapple with a message that will change him forever," reads the film's official synopsis.
"Based on Pulitzer Prize-winning author William Saroyan's 1943 novel The Human Comedy, Ithaca is a coming-of-age story about the exuberance of youth, the abruptness of change, the sweetness of life, the sting of death, and the sheer goodness that lives in each and every one of us," it continues.
With an original score by John Mellencamp, Ithaca is set to arrive in theaters Sept. 9.
Ryan and Hanks famously starred together in three hit romantic comedy's throughout the '90s including Joe Versus the Volcano, Sleepless in Seattle and You've Got Mail.