A physician (urologic oncologist) scientist, Theodorescu's pioneering application of computational biology led to the discovery of genes that drive bladder and other cancers, while providing novel biomarkers and therapeutic targets. In 2023 his lab was the first to demonstrate that loss of the Y chromosome in cancer makes tumors more aggressive by allowing them to evade the immune system. In 2025 he showed that loss of Y chromosome in cancer patients' T cells adversely affects tumor outcome, and this further promotes aggressive behavior in cancers which have already lost the Y chromosome. These findings shed light on novel angles of therapeutic development as well as having significant implications for cellular therapies such as CAR-T. He developed novel concepts in personalized/precision such as the Artificial Intelligence based Multi-Omic approach called Molecular Twin Precision Oncology Platform (MT-POP) and the COXEN (CO-eXpression ExtrapolatioN) algorithm that uses gene co-expression patterns from in vitro cancer cell lines to extrapolate and predict clinical responses in patient tumors. The latter was tested in a national prospective clinical trial with encouraging results. He led the discovery and development of a “first in class” RalGTPase inhibitor as a new therapeutic in several human cancer types now commercially licensed. Theodorescu is a founding co-editor in chief of Bladder Cancer, the first journal focused on this disease and the Director of the Convergent Science Virtual Cancer Center (www.csvcc.org), a pioneering initiative designed to accelerate cancer research by fusing insights across disciplines in a mentorship-driven ecosystem for early-career scientists tackling cancer from fresh, integrative angles. His laboratory is currently funded by multiple federal grants including an R35 Outstanding Investigator Award (OIA) from the National Cancer Institute (NCI). He has been elected to societies including the American Society for Clinical Investigation (ASCI), Association of American Physicians (AAP), the American Association of Genitourinary Surgeons (AAGUS), the American Surgical Association (ASA) and the National Academy of Medicine (NAM).He is an Honorary Fellow of the American Association for the Advancement of Science (AAAS).