Her mother was the first self-identified African-American woman to be accepted at Vassar College[6] and to earn a degree from the Yale University School of Medicine.

[18] In 1991 Hamburg was appointed Commissioner of the New York City Department of Health and Mental Hygiene, where she served for six years, working first for Mayor David Dinkins and then-Mayor Rudy Giuliani.

[19] In 1997, President Bill Clinton appointed Hamburg as Assistant Secretary for Planning and Evaluation at the U.S. Department of Health and Human Services.

In that role, Hamburg spearheaded efforts to prevent, detect, and respond to both naturally occurring and deliberately caused biological threats.

In June 2001, Hamburg participated in the Operation Dark Winter exercise at Andrews Air Force Base simulating a bioterrorism event involving weaponized smallpox.

[22] On July 13, 2005, she was announced as an advisor to the Project on Emerging Nanotechnologies by the Pew Charitable Trusts and Woodrow Wilson International Center for Scholars.

[27][28][29][19] During Hamburg's tenure at the FDA, the agency was criticized for speeding approvals at the expense of safety, while some industry voices indicated the pace was "justified".

In 2018, she participated in the Clade X pandemic exercise that modelled a fictional parainfluenza bioterrorism attack designed to reduce the global population.

Other notable participants included Peter Daszak of EcoHealth Alliance, Jeremy Farrar of Wellcome Trust, and representatives from the National Institutes of Health, Rockefeller Foundation, London School of Hygiene & Tropical Medicine, ExxonMobil, University of Hong Kong, Burroughs Wellcome Fund, World Health Organization, African Development Bank, Robert Wood Johnson Foundation, National Oceanic and Atmospheric Administration, and numerous universities.

[37] Additionally, Hamburg was appointed by the Council on Foreign Relations to serve on its Independent Task Force on Improving Pandemic Preparedness, co-chaired by Sylvia Mathews Burwell and Frances Fragos Townsend.

[38] That year, she also served on the CSIS-LSHTM High-Level Panel[39] on Vaccine Confidence and Misinformation amid the COVID-19 pandemic, co-chaired by Heidi Larson and J. Stephen Morrison.

[40] Hamburg participated in a tabletop exercise at the March 2021 Munich Security Conference modelling a fictional international outbreak of monkeypox.