[4] Cusack returned to America, and on December 12, 2006, joined the Chicago production of Wicked as the standby for the lead role of Elphaba.

Impressed with her portrayal of the character, the producers asked her to star in the lead role on the show's first national tour, beginning in November 2007.

[8][9] In 2012, she played the role of Miss Gardner in the Off-Broadway revival of Carrie: The Musical, which began performances at the Lucille Lortel Theatre on January 31, 2012.

[12] Cusack appeared as Dot/Marie in the Chicago Shakespeare Theater production of Sunday in the Park with George from September 26 to November 4, 2012, opposite Jason Danieley.

[16] Cusack portrayed Clare Boothe Luce in the new musical Flying Over Sunset, directed by James Lapine.

[21] In July 2022, Cusack starred as Mrs. Lovett in The Muny production of Sweeney Todd: The Demon Barber of Fleet Street.

[22] Cusack originated the role of Alice Murphy in the new musical Bright Star, written and composed by Steve Martin and Edie Brickell.

[29] Cusack reprised the role of Alice during the musical's North American tour stops in Los Angeles,[30] San Francisco,[31] and Salt Lake City.

[32] In 2018, Cusack appeared as Sabrina in James Ponsoldt's critically acclaimed Facebook Watch dramedy Sorry for Your Loss and was cast opposite Tom Hanks in Marielle Heller's Fred Rogers biopic A Beautiful Day in the Neighborhood.