A faculty member since 1988, his research interests include optimization, stochastic systems, machine learning, and their application. In recent years, he has worked in robust optimization, statistics, healthcare, transportation and finance. Bertsimas was a cofounder of Dynamic Ideas, LLC, which developed portfolio management tools for asset management. In 2002, the assets of Dynamic Ideas were sold to American Express. He is also the founder of Dynamic Ideas Press, a publisher of scientific books, the cofounder of Benefits Science, a company that designs health care plans for companies, of Dynamic Ideas Financial, a company that provides financial advice to customers, of Alpha Dynamics, an asset management company, P2 Analytics, an analytics consulting company and of MyA health, a personalized health care advice company.

Bertsimas has coauthored more than 200 scientific papers and the following books: Introduction to Linear Optimization (with J. Tsitsiklis, Athena Scientific and Dynamic Ideas, 2008); Data, Models, and Decisions (with R. Freund, Dynamic Ideas, 2004); Optimization over Integers (with R. Weismantel, Dynamic Ideas, 2005); and The Analytics Edge (with A. O'Hair andW. Pulleyblank, Dynamic Ideas, 2016). He is former department editor of Optimization for Management Science and of Operations Research in Financial Engineering. Bertsimas has supervised 59 doctoral and 31 Master students. He is currently supervising 22 doctoral students. A member of the National Academy of Engineering and an INFORMS fellow, he has received numerous research awards, including the Harold Larnder Prize (2016), the Philip Morse Lecturship prize (2013), the William Pierskalla best paper award in health care (2013), best paper award in Trapsoration (2013), the Farkas Prize (2008), the Erlang Prize (1996), the SIAM Prize in Optimization (1996), the Bodossaki Prize (1998), and the Presidential Young Investigator Award (1991–1996). He has also received recognition for his educational contributions: The Jamieson prize (2013) and the Samuel M. Seegal prize (1999).