Abstract Patients and healthcare providers are important partners in cancer biobanking and research. Until now, however, there have been a limited number of scalable approaches to engage patients and providers as true collaborators in biobanking studies. The National Cancer Institute's Cancer Moonshot Biobank is a new engagement-centered project whose goal is to accelerate cancer research on drug resistance and sensitivity. This ambitious undertaking will involve the collection and distribution of longitudinal cancer biospecimens from over 1000 research participants receiving standard of care therapy at participating NCI Community Oncology Research Program (NCORP) institutions. Participants will be asked to donate blood and tissue at various time points including at baseline, during treatment, and at progression, if applicable. Engagement is a core component of the project given the longitudinal nature of the project, and the importance of participants and providers to its success. We define engagement as the establishment of an ongoing trusting and mutually vested relationship between study participants, healthcare providers and the Biobank. The three main engagement components of the Cancer Moonshot Biobank are: 1. External Scientific Panel (ESP): An extramural team of physicians, patient advocates, communication and biobanking experts who give input on various aspects of Biobank engagement 2. Local engagement activities at NCORP Sites 3. An online Participant and Provider Engagement (PPE) portal The PPE portal will be the main platform for direct interface between the Biobank and its participants, healthcare providers, as well as the public, and will serve as an archetype within NCI for the development of a unified portal for future NCI projects. Through the PPE portal, participants and providers will receive program updates, securely access documents including their biomarker test results and signed consent forms, and access educational material and other community resources. We describe ideation, design, and content creation for the PPE portal. Strategies for usability testing, integration of feedback, procedures for design and content iteration, as well as lessons learned are also discussed. Through the creation of NCI's PPE portal we aim to provide a valuable resource to participants and providers who are part of the Cancer Moonshot Biobank, while at the same time facilitating adoption of online engagement strategies within NCI and beyond. Citation Format: Esmeralda Casas-Silva, Helena J. Ellis, Veena Gopalakrishnan, Carol J. Weil, Abhi Rao, Lokesh Agrawal, Ping Guan, Natalie Madero, Jane W. Wanyiri, Jeffrey McLean, Mark A. Jensen, James Suh, Sean McDermott, P. Mickey Williams, Helen M. Moore, Laura Kadamus, Ainsley Adao, Rhett Beattie, Frank Ali, Debapriya Sarkar. Fostering research participation through NCI's Cancer Moonshot Biobank engagement portal [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4352.