She began working with ICRW in 1988 as a consultant, researcher, and officer, and headed the private, non-profit organization based in Washington, D.C., from 1997 through April 2010.

Appointed by United Nations Secretary-General Ban Ki-moon, she served as deputy executive director for UNICEF and the vice chair of the board for the GAVI Alliance from 2011 to 2016.

At the Tata Institute of Social Sciences, Rao Gupta worked with a team to develop the first women's studies curriculum for graduate students in India.

In the 1990s, Rao Gupta headed a ground-breaking, 15-country research program that identified the social and economic roots of women's vulnerability to HIV infection.

Rao Gupta currently serves as co-convener of the Social Drivers Working Group of aids2031, an international initiative commissioned by UNAIDS to chart a course for a global response to AIDS over the next twenty-five years.

[7] Rao Gupta is often sought by the development community and media, and has been quoted by the Washington Post, The New York Times and USA Today, as well as other national and international news sources.

[10] Gupta was renominated by President Biden in the 118th Congress, and her nomination was advanced by the United States Senate Committee on Foreign Relations on March 8, 2023.