Karam has said that seeing both her parent's praying and nanny's puja from a young age sparked her interest in religion and religious collaboration.

Thereafter, from 2007 to 2019, she worked at the United Nations Population Fund (UNFPA) serving as Senior Advisor on Culture.

[1][7] In 2019, she was elected as the first woman, first Muslim and first North African to hold the position of Secretary General at Religions for Peace in the organization's 50-year history.

[9] Karam taught as a lecturer at the School of Politics at the Queen's University of Belfast, Northern Ireland from 1998 to 2000.

[12] In 2024, Karam became an affiliate professor at the Ansari Institute for Global Engagement with Religion at Notre Dame University in South Bend, Indiana.