Hanks' soon became known as a romantic leading man with his films with Meg Ryan, Joe Versus the Volcano (1990), Sleepless in Seattle (1993), and You've Got Mail (1999).

During the 1990s he excelled in critically acclaimed dramas such as Penny Marshall's A League of Their Own (1992), Jonathan Demme's Philadelphia (1993), Robert Zemeckis' Forrest Gump (1994), Ron Howard's Apollo 13 (1995), Steven Spielberg's Saving Private Ryan (1998), and Frank Darabont's The Green Mile (1999).

Since the turn of the 21st century, Hanks' continued working in dramatic films, including Cast Away (2000), Road to Perdition (2002), Catch Me if You Can (2002), The Terminal (2004), Charlie Wilson's War (2007), Cloud Atlas (2012), Captain Philips (2013), Saving Mr. Banks (2013), Bridge of Spies (2015), Sully (2016), The Post (2017), A Beautiful Day in the Neighborhood (2019), Greyhound (2020), and News of the World (2020).

He is also known for his work as a producer and director on various television series including From the Earth to the Moon (1998), Band of Brothers (2005), John Adams (2008), and The Pacific (2009).

In 2013, he made his Broadway debut in Nora Ephron's Lucky Guy earning a Tony Award for Best Actor in a Play nomination.