ABSTRACT In 2017, the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) was among the first recipients of the National Cancer Institute (NCI) Youth Enjoy Science (YES) Research Education Program (R25) grant, launching Chicago EYES (Educators and Youth Enjoy Science) on Cancer. This is a resubmission application addressing minor criticisms from a 2022 competitive renewal submission that received a score of 14 providing more details on research skill development, trainee participants, programmatic consideration of different populations and mentor training that specifically addresses the needs of the populations we serve. EYES serves high school students, college students, and high school science teachers from across Chicago, engaging them in cutting-edge cancer research, science education, and biomedical career exploration. To date, the program has enrolled 70 student trainees from backgrounds underrepresented in the sciences and 14 teacher research fellows from underserved communities. Evaluation data reflect growth in trainees’ research skills and expertise; knowledge and self-confidence regarding research professions; and commitment to pursuing a research career. Ninety-six percent of student alumni remain committed to careers in STEM, and more than a third are pursuing a cancer specialization. Teacher research fellows described their experience as transformational, imparting new insights about science learning and practice that not only strengthened their skills as educators, but also improved their ability to relate to their students. Renewed funding is essential to build on the success of EYES. Specifically, we aim to: 1) Equip young people with specialized skills and expertise to build their competencies as entry-level cancer researchers; 2) Broaden young people’s awareness of cancer-related career opportunities and empower them to make informed, strategic plans to accomplish career goals; 3) Strengthen support for young people’s career development by engaging members of the scientific and local communities, and young people’s immediate families, in their education and training; and 4) Maintain a robust network of support for program alumni. Over the next five years, we expect to enroll at least 70 new high school and college students, and at least 8 teacher research fellows, in the full two-year program. Through our partnerships with Chicago Public Schools, the Museum of Science and Industry, Chicago Access Network Television, and other local institutions, we anticipate engaging more than 1000 community members each year in STEM enrichment and outreach activities. In these ways, Chicago EYES on Cancer will continue to empower the city’s diverse and talented youth to pursue careers in biomedicine, supporting NCI’s mission to build a diverse cancer workforce, advance scientific knowledge, and help all people live longer, healthier lives.