: The recent pandemic dramatically highlighted the need for a well-trained, highly adaptable clinical and translational science workforce; especially one that is capable of rapid design and deployment of clinical trials and key capabilities that accelerate research translation. The University of Texas Health Science Center at Houston (UTH-H), The University of Texas MD Anderson Cancer Center (MDACC) and their partner institutions across Texas, have collective capabilities and relationships that allow us to meet these profound and critical career development needs. Based at McGovern Medical School, the K12 emphasizes T2-T4 science and serves our Schools of Public Health, Biomedical Informatics, Nursing, and Dentistry, MDACC, and our partner institutions: Rice University, UT Rio Grande Valley, UT Tyler and Texas Tech Health El Paso. We propose to fund five Scholars per year, leveraging CTSA funding to enhance the program by developing skilled clinical and translational (C&T) investigators in the Texas Medical Center (9,200 beds; 10 million encounters per year) and the three geographically dispersed medical centers that comprise our partners. Our program includes: 1) the C&T Research Curriculum (11 required courses/workshops, provided in person and online); 2) MS courses and degree in Clinical Research (optional for Scholars and tailored to individualized career development; and 3) the Intensive Mentorship Program, our central focus, which has been highly successful in helping KL2 and other mentees secure major grants, publish in high impact journals, and become institutional and national academic leaders. Additional impact includes our Scholars’ success in improving the delivery, safety, and effectiveness of healthcare to various segments of the population; advancing research methods using n-of-1 trials, Bayesian methods, hybrid implementation effectiveness designs and economic analyses; and showing reduced health system costs to secure clinical reimbursements that sustain and expand improved approaches to health care. Next cycle innovations will augment these strengths, specifically train the NCATS-identified translational science competencies and promote learning health care (LHC) through an expanded LHC consultation service emphasizing comparative effectiveness studies, implementation and de-implementation research, a continuous community engagement program, and IRB leadership to facilitate and advance exemplary clinically embedded studies and trials of emergency therapies. These and other Core features will promote the career development of Scholars within an LHC system to rapidly advance clinical care and improve the health of all populations. Integration with the UM1 and the T32s is synergistic. With our successful track record, infrastructure, and institutional support, CTSA funding will produce a substantial return by developing innovative, collaborative, rigorous, and productive leaders in C&T science.