ABSTRACT The goal of the Pilot Project Program is to support the mission of the Centers of Biomedical Research Excellence (COBRE) Center for Molecular Epidemiology at Dartmouth, to advance transformative discoveries to reduce the burden of human disease and develop future leaders in the field. To date, the Pilot Project Program has supported 15 pilot projects led by early-stage, mid-career, and senior investigators that have contributed to the Center themes of i) applying new scientific discoveries and technologies to address major health concerns, ii) identifying early indicators of disease pathogenesis, and iii) exploring common pathways of disease etiology and progression in human populations, including those related to health inequities. Pilot Project Leaders have published 326 peer-reviewed manuscripts and received 52 extramural grants as Principal Investigators, totaling $85.8 million dollars. Building on the success of our work in Phases I and II, and by incorporating feedback from external advisors and previous pilot awardees, we propose to enhance the Pilot Project Program in Phase III to accelerate the career trajectories to scientific discovery and extramural support of talented scientists in the field of molecular epidemiology. Applicants will be solicited through multiple media and channels for three funding opportunities: 1) new and early-stage investigator projects to expedite career development and research independence; 2) multi-PI projects that promote multi-disciplinary team science leading to larger program and center grants; and 3) multi-institution projects that strengthen collaborations with partnering IDeA states. We will encourage applicants from underrepresented groups and facilitate research that addresses the health of vulnerable populations, considers biological sex as potential modifier of disease risk, and benefits from the Center’s state-of-the-art Biorepository and Biospecimen Resource Facility Core. We also will allow for a fast-track mechanism of time-sensitive, high-risk, high-reward applications. A letter of intent will be requested to screen for eligibility and permit pre-application mentoring. Applications will be ranked by a review panel using the criteria and processes of NIH study sections, followed by funding recommendations by the External Advisory Committee prior to submission to the NIH for final approval. Post-award mentorship and holistic career development offerings will be tailored to the Pilot Leaders’ goals, scientific focus, and career stage. Opportunities will be responsive to member surveys and guidance from the Steering and Advisory Committees. Thus, our strategy will provide Pilot Leaders with the necessary preliminary data, mentorship, and training to compete for multiple grant mechanisms, and to grow impactful independent and collaborative research programs in molecular epidemiology.