His research is focused on understanding why HER2-positive breast cancer sometimes resists targeted therapies and on the development of new treatment strategies for breast cancer. He has led clinical trials using new therapies to overcome resistance in people with breast cancer. Dr. Esteva is also interested in finding new ways to predict diagnosis and outcomes of breast cancer.

Dr. Esteva maintains an active clinical practice and has served as the principal investigator or co-investigator in over 100 clinical trials in breast cancer. In addition, Dr. Esteva has served as reviewer for grant committees and peer-reviewed journals, including the Journal of Clinical Oncology, Clinical Cancer Research, Cancer Research, and Cancer. He has received prestigious research awards from federal agencies and private foundations, and he is widely published in oncology journals. He is one of the editors of the textbook, Advanced Therapy of Breast Disease, currently on its third edition.