She is best known for her role as Daphne Hatzilakos in the teen drama series Degrassi: The Next Generation (2002-2010) and as the host and showrunner of her own syndicated television program Out There with Melissa DiMarco.

DiMarco's TV credits include the CBC soap opera Riverdale and guest-starring spots on series such as Due South, Blue Murder, The Hardy Boys, Psi Factor, Kung Fu: The Legend Continues, Relic Hunter, and Kojak.

[2] She also directed, produced, and wrote Dreamseeker: Nia Vardalos, an award-winning documentary on the rise of Nia Vardalos[3] of My Big Fat Greek Wedding fame and was the host and producer of Nite Life, an entertainment show that focused on celebrity interviews and the nightclub, bar, and concert scene, which aired on OMNI.

[6] The show mixes celebrity interviews with scripted comedy that takes a behind-the-scenes look at the life of an entertainment journalist (played by DiMarco).

Among the celebrities she has interviewed on the show are Pierce Brosnan, George Clooney, Cameron Diaz, Colin Farrell, Salma Hayek, Queen Latifah, Ludacris, Matthew McConaughey, Brad Pitt, and Gene Simmons.