The Chicago Cancer Health Collaborative (ChicagoCHeC) is a comprehensive partnership to advance solution-oriented approaches to cancer health disparities. ChicagoCHeC brings together the synergistic strengths of two public institutions, the University of Illinois at Chicago (UIC) and Northeastern Illinois University (NEIU), with a world class NCI-designated comprehensive cancer center – the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (NU-LCC). ChicagoCHeC combines the attributes of these three exceptional institutions, each with robust capacity to interact with their urban-shared setting. Launched in 2015, ChicagoCHeC is dedicated to addressing cancer health disparities through rigorous and innovative science, education, and outreach and engagement with Chicago’s communities. This is reflected in the following goals: Aim 1. To strengthen a transformational alliance between UIC, NEIU, and the NU-LCC to address cancer health disparities in Chicago; Aim 2. To initiate, conduct, and support innovative bench, translational, clinical, and prevention and control focused cancer research, with emphasis on cancer health disparities; Aim 3. To develop and implement cancer-related education and outreach activities generated with the engagement of communities across Chicago; Aim 4. To coordinate research education and mentoring opportunities for students preparing to become future biomedical scientists and to develop early career faculty who will forge independent cancer research careers; and Aim 5. To conduct ongoing rigorous evaluation of ChicagoCHeC activities. These goals are accomplished by a nurturing hub of four Cores (Administrative, Planning and Evaluation, Research Education, and Outreach) and a research project funding program. Since the launch of ChicagoCHeC in 2015, there has been rapid growth in collaborative infrastructure built across the three partnering institutions; enhanced cancer research engagement, capacity, and education; extensive community outreach and engagement; and encouraging advancement of ChicagoCHeC faculty and students. ChicagoCHeC projects and programs provided research experiences to 155 students, provided cancer research and leadership opportunities for 57 faculty, and directly resulted in 94 peer-reviewed publications, 47 extramural grants submitted, and 24 grants awarded. ChicagoCHeC will leverage the momentum forged by the initial U54 award to drive innovative cancer research, research education, and community outreach and engagement that cuts across disciplinary and institutional boundaries. ChicagoCHeC will leverage its exceptional team of faculty, students, and partners, connectivity to Chicago’s communities, and guidance of internal and external advisory bodies. The next chapter will include two initial full cancer research projects and two initial pilot projects, continued support from four tri-institutional ChicagoCHeC Cores, and strong institutional commitment.