Abstract Introduction: Rising obesity rates significantly contribute to increases in many types of cancer. The link between obesity, socioeconomic status, and cancer risk is evident, particularly in persistent poverty areas. The Acres Homes Cancer Prevention Collaboration (Acres Homes CPC), part of the Persistent Poverty Initiative (PPI) of the National Cancer Institute, is a dynamic partnership led by the University of Texas MD Anderson Cancer Center. This community-academic partnership, centered on the Acres Homes neighborhood in Houston, TX, that is impacted by persistent poverty, utilizes community-engaged strategies and transdisciplinary research to mitigate obesity-related cancer risks. Methods: Through multiple community partnerships, the CPC aims to alleviate persistent poverty effects, support early-career researchers, and test nutrition and physical activity interventions for reducing obesity-related cancer risk. Results: The Acres Homes CPC funds two research projects: a trial of a physical activity program for cancer survivors and a cluster-randomized trial of food distribution and nutrition education for elementary school children and their parents. We have funded seven pilot studies on topics such as food security, culinary medicine, physical activity and mild cognitive impairment, and the physical and safety environment of neighborhoods. Three community advisors guide and support all activities, and information on the initiative is provided monthly to a community steering committee. The Acres Homes CPC also supports pre- and postdoctoral fellows interested in research promoting cancer prevention and control in persistent poverty communities. Conclusions: This initiative aims to reduce cancer risk and improve cancer outcomes in persistent poverty communities by bridging the gap between research and practical implementation through community-based participatory research and partnership with the community to address obesity. Citation Format: Karen Basen-Engquist, Ruth Rechis, Michael Mackert, Brad Love, Shreela Sharma, Sanjay Shete, Qian Lu, Shine Chang, Margaret Raber, Miranda Baum, Crystal Roberson, Lorna McNeill. Partnership in persistent poverty neighborhoods: The Acres Homes Cancer Prevention Collaboration [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B130.