Messina's film appearances include Vicky Cristina Barcelona (2008), Julie & Julia (2009), Devil (2010), Argo (2012), Ruby Sparks (2012), Celeste and Jesse Forever (2012), Cake (2014), Birds of Prey (2020), I Care a Lot (2020), Call Jane (2022), Air (2023), and The Boogeyman (2023).

Messina was raised in Northport, New York, on Long Island, where he studied theater in high school.

He had a recurring role in the fifth and final season of the HBO drama series Six Feet Under as Ted Fairwell.

[7] Messina was a series regular on the Fox/Hulu sitcom The Mindy Project, playing Dr. Danny Castellano, until his character was eventually phased out in seasons 4 and 5.

That same year, he directed the independent drama, Alex of Venice, starring Mary Elizabeth Winstead, Don Johnson and Matthew Del Negro.

In 2018, Messina starred in a leading role alongside Amy Adams in the HBO series Sharp Objects.