She is most notable for her series regular role as Lola, a "trans-truther", on the second and third seasons of the Hulu television program Difficult People, on which she was also a writing consultant.

She went on to pursue an MFA in Experimental Choreography and Ph.D. in Critical Dance Studies at University of California Riverside.

Nayfack was a founding member and artistic director of New York's Musical Theatre Factory, and her one-woman show Manifest Pussy was highly regarded by the Manhattan theater scene.

[3] In 2015, she received the Lilly Award, which supports women in the theater and promotes gender parity for theatrical productions, in the "working miracles" category.

[6] She plays the role of Ava in the 2019 musical finale of Amazon show Transparent, directed by Joey Soloway.