[1][2] Following the resignation of Rochelle Walensky, Shah served as the acting director of the U.S. Centers for Disease Control and Prevention in July 2023 until Mandy Cohen assumed office.

[5][8][6] In 2001, Shah accepted a Henry Luce Scholar fellowship in Phnom Penh, Cambodia, working for the Ministry of Health as an economist and epidemiologist.

In a March 2021 interview, he credited his experiences in Cambodia, as well as his ongoing communication with colleagues in Southeast Asia, with his ability to help prepare Maine for COVID-19 as its state CDC director, especially relating to the early procurement of personal protective equipment.

While completing both medical and law school, he regularly videoconferenced with colleagues in Southeast Asia and occasionally traveled back to Cambodia.

[5][10][7] During his tenure, Shah worked on initiatives combatting the opioid crisis in Illinois, addressing childhood lead poisoning, and reducing maternal and infant mortality.

Although Shah maintains that the agency followed all federal guidelines and moved quickly: "The Illinois Department of Public Health (IDPH) did not go on-site at Quincy Veterans’ Home until midday on Monday, August 24.

[10] As the pandemic developed, Shah received praise for his communication style, delivering information using measured, detailed and simple answers, real-life examples, and effective metaphors devoid of scientific jargon.

[10][5][17] For example, when asked to detail proper hand washing techniques to prevent the spread of COVID-19, Shah explained “Wash your hands as if you have just sliced a bag of jalapeño peppers and now need to take out your contact lenses.”[13] Shah embraced three principles for his regular briefings: Be truthful, answer questions directly, and "acknowledge the statistics and numbers without overlooking the human element.

"[12] Public health experts praised his enduring compassion[10][17] as he consistently reminded viewers that each case number and death represented a family member, friend and neighbor.