Diabetes mellitus is a significant health burden, and recent reports indicate an increase in diabetes-related complications in the United States (U.S.). The mission of the National Institute of Diabetes and Digestive and Kidney Diseases Centers for Diabetes Translational Research (CDTR) is to improve the translation of research findings in diabetes prevention and treatment by supporting research across the translational science spectrum. To facilitate this mission, it is imperative to support multidisciplinary translational early-stage investigators (ESIs) to address the societal-, environmental-, and individual-level factors that impact diabetes outcomes. In this special communication article, we characterize the challenges, opportunities, and needs of ESIs transitioning to mid-careers whose goals are to develop a career in diabetes translational research. These challenges and opportunities were collected from 34 ESIs and 19 senior faculty members from 23 institutions across the U.S. who attended the inaugural CDTR National Enrichment Program Conference. Our findings aim to promote the engagement of ESIs in diabetes translational research and provide guidance in strengthening and sustaining their research careers.