ABSTRACT The Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins is dedicated to cancer research, education and training, and patient care, with the overarching goal of creating and applying new knowledge to improve prevention, screening, detection, diagnosis and treatment of cancer in Maryland (the SKCCC catchment area) and throughout the nation and the world. This application seeks continued Cancer Center Support Grant (CCSG) funding for SKCCC Research Programs and Shared Resources (SRs). Since the previous CCSG renewal in 2016, the SKCCC has eliminated three Research Programs and created one new Program. Now, the 285 Members, from 34 academic departments throughout Johns Hopkins University, populate seven Research Programs: the new Cancer Invasion and Metastasis Program, and the established Programs in Cancer Genetics and Epigenetics, Cancer Immunology, Cancer Molecular and Functional Imaging, Cancer Chemical and Structural Biology, Hematologic Malignancies and Bone Marrow Transplantation, and Cancer Prevention and Control. Twelve SRs provide state-of-the-art-or-better support for SKCCC research and researchers. SKCCC science encompasses discovery research into the molecular genetics and epigenetics of human tumorigenesis, clinical trials of new immunotherapies and other cancer treatments, and epidemiologic analyses of lifestyle influences on cancer mortality. Over the past funding period, SKCCC Members were exceptionally productive, authoring 3,775 publications (23% Intra- Programmatic, 22% Inter-Programmatic and 66% featuring external collaborators). SKCCC researchers garnered $78.5 million in current peer-reviewed grant support, including $44.9 million from the National Cancer Institute. The SKCCC continued to deliver its science to the bedside. From an average 6,374 new cancer patients treated per year from 2016–2020, an average of 1,647 new subjects were enrolled annually to interventional studies (26% of newly registered cancer patients); therapeutic studies accrued some 17% of cancer patients. In addition, the SKCCC has worked successfully to promote inclusion of minority and underserved patients with cancer in clinical research, yielding a slight increase in minority participation in interventional trials (22.3% in 2015 to 25.4% in 2020), while African American accrual to interventional trials remained steady (15.0% in 2015 and 15.6% in 2020). Moving forward, the SKCCC plans: (1) to promote new breakthroughs in fundamental cancer research that create paradigm-shifting insights into the nature of human cancers, (2) to translate this pipeline of discovery into practice-changing advances, (3) to overcome barriers responsible for disparities in cancer outcomes by enhancing the delivery of innovative cancer services throughout the state of Maryland catchment area, and (4) to integrate research training and career development of biomedical scientists and health care professionals into all cancer research endeavors.