In 2005, Bomer made his film debut in the thriller Flightplan, then in 2007 gained recognition with his recurring role in the NBC television series Chuck.

Bomer had supporting roles in the 2011 thriller In Time, the 2012 comedy-drama Magic Mike and its 2015 sequel, and the 2016 neo-noir film The Nice Guys.

He has since starred as Larry Trainor in the Max series Doom Patrol (2019–2023) and a closeted World War II veteran in the miniseries Fellow Travelers (2023).

On stage, Bomer starred in the Dustin Lance Black play 8 on Broadway, and at the Wilshire Ebell Theatre in Los Angeles as Jeff Zarrillo, a plaintiff in the federal case that overturned California's Proposition 8.

[3] Bomer was raised in Spring, Texas, and attended Klein High School; he was a classmate of Lee Pace and Lynn Collins.

His screen debut occurred in the 2005 starring in the Robert Schwentke directed mystery thriller Flightplan,[23] opposite Jodie Foster.

[32] In 2007, Bomer took on the role of Ernest Hemingway in a Williamstown Theatre Festival production of Crispin Whittell's play Villa America in Massachusetts, starring in it with Jennifer Mudge and Nate Corddry.

[33][34] 2009 marked a significant turning point in Bomer's career as he starred as the con artist Neal Caffrey in the police procedural drama series White Collar.

Mary McNamara of the Los Angeles Times wrote: "terrific acting, crackling dialogue and geek-hip crime are not the only things that make this the most electric drama to premiere this fall.

In the beginning of 2010 Bomer was invited to sing with actress and Tony Award winning singer Kelli O'Hara at the Kennedy Center Honors.

[40] In September 2011, Bomer starred in Dustin Lance Black's play, 8, a staged re-enactment of the federal trial that overturned California's Proposition 8.

[43][44] In 2011, Bomer was cast as a 105-year-old man in Andrew Niccol's science fiction thriller film In Time, starring alongside Justin Timberlake.

[45] On April 10, 2012, Bomer made a guest appearance in the third season of the television series Glee, playing Blaine's older brother, Cooper Anderson, a Hollywood commercials actor who comes to Lima for a visit, and while in town gives an acting masterclass to New Directions.

The first was as a guest performer on the NBC sitcom The New Normal, portraying the role of Monty, the ex-boyfriend of the protagonist of the series, Bryan Collins, played by Andrew Rannells.

[59] Bomer's next project involved Ryan Murphy casting him opposite Mark Ruffalo, Jim Parsons and Julia Roberts in the drama romance film The Normal Heart (2014).

Based on Larry Kramer's play of the same name, it featured Bomer as a closeted writer of The New York Times and love interest of Ruffalo's character.

[60] The film shows the rise of the HIV-AIDS crisis in New York City between 1981 and 1984, as seen through the eyes of writer/activist Ned Weeks (Ruffalo), the founder of a prominent HIV advocacy group.

[62] Matthew Gilbert of The Boston Globe praised that Bomer is: "quite simply, devastating in this movie, his beauty adding resonance because it begins to fade so suddenly, as his cheeks protrude and lesions gather."

[68] Bomer's first release of 2015 was Magic Mike XXL, a sequel to the popular 2012 film, again featuring Channing Tatum and Joe Manganiello.

[69] Reviewing the film for Rolling Stone, Peter Travers noted that; "the movie is just a rambling, loosey-goosey road trip, with Bomer and Manganiello getting extra time to shine.

[75][76] His next role was as Matthew Cullen in Antoine Fuqua's Western action film The Magnificent Seven,[77] playing the farmer husband of Haley Bennett's character.

[78][79] He was cast as Monroe Stahr, the lead in Billy Ray's 2016 series The Last Tycoon, loosely based on the F. Scott Fitzgerald novel of the same name, along with actors Kelsey Grammer, Lily Collins, and Dominique McElligott.

[81] Justin Chang of Los Angeles Times noted that he "steps confidently into the boots of a rugged, know-it-all mountain man whose idea of tough love can turn unexpectedly toward tenderness around a flickering campfire.

"[82] David Ehrlich of IndieWire stated that Bomer fortunately plays against his "pretty boy type so convincingly that you might forget where you've even seen him before",[83] concluding that Bomer "gives a commanding performance in a movie that fails to realize how evocative he is, the Smiths defaulting to flashbacks that show us less about cowboys and gender codes than we can glean from the wild look in its lead actor's face.

[85] Bomer was cast as Freda Von Rhenburg, a transgender sex worker who lives in Los Angeles and begins a relationship with her neighbor, Early Landry (played by John Carroll Lynch).

[91] He found a part in a 2018 revival of the Mart Crowley play The Boys in the Band, which was staged at Booth Theatre and marked his Broadway debut.

[93] Directed by Joe Mantello, it tells the story a group of gay men who gather for a birthday party in New York City.

[94] Theater critic Michael Sommers noted that "Matt Bomer tends to fade in the glare of flashier personalities, but he lends the character a watchful quality as one of those deferential souls who is content to observe others.

[98] A reviewer for Screen Daily argued that Bomer is "terrific" and concluded that "while he may not yet have the name recognition to act as a key selling point for this film, it's the kind of performance which gets noticed".

[105] Bomer joined the cast of the Academy Award for Best Picture nominated film Maestro in March 2022 where he played the role of David Oppenheim and starred alongside Bradley Cooper and Carey Mulligan.