[4] From 2012 to 2016, Rodriguez began to work on stage again and appeared in small television roles, including Nurse Jackie, The Carrie Diaries, and Luke Cage.

Walker-Browne asked Rodriguez to read for the part of Angel and helped her to land an audition in an upcoming off-Broadway production of Rent.

Beginning with hormone replacement therapy in early 2016,[4] and allowing sufficient time for privacy, Rodriguez reemerged as an actress.

[4][19] She then appeared in several additional stage productions: Rodriguez also landed a supporting role in the independent film Saturday Church as Ebony.

The 2017 film, which premiered in January 2018, depicted a runaway teenager exploring their gender identity and becoming involved in the contemporary underground ball culture scene.

[25] The show was created by Ryan Murphy, Brad Falchuk, and Steven Canals and made history by casting five transgender actresses in leading roles.

[26][27][28] The series is set in New York City during the 1980s and explores the lives of queer people of color (especially Black trans women) who are involved with the underground ballroom scene.

[7][30][31][32] Among the show's regular cast are Rodriguez's Saturday Church co-star Indya Moore, Tony Award-winner Billy Porter, model Dominique Jackson, trans rights advocate Angelica Ross, Evan Peters, Kate Mara, and James Van Der Beek.

Rodriguez performed with Pose co-stars Dyllón Burnside, Billy Porter and Ryan Jamaal Swain in a benefit concert on July 23, 2018, to celebrate the season 1 finale and raise money for GLSEN and sing "Waving Through a Window" from Dear Evan Hansen.

Her cast mates included George Salazar (from Broadway's Be More Chill) as Seymour and Amber Riley (Glee) as Audrey II.

[39] On May 7, 2021, it was reported by Variety that Rodriguez would star alongside Maya Rudolph in Apple TV's upcoming comedy series directed by Alan Yang and Matt Hubbard.