Purpose <p>National Cancer Institute-designated Cancer Center Community Outreach and Engagement (COE) teams are expected to collect data to describe their catchment area’s cancer burden. University of Iowa Health Care Holden Comprehensive Cancer Center employed a mixed-methods approach to describe rural–urban differences.</p> Methods <p>We conducted descriptive analyses of cancer registry data to characterize cancer incidence, mortality and five-year survival in our cancer center’s catchment area. We used secondary data sources to identify cancer risk/protective factors. All analyses were stratified by rurality using Rural-Urban Continuum Codes. Rural cancer leaders were interviewed to gain local perspectives on rural cancer burden and resiliencies.</p> Results <p>Rural counties had higher incidence compared to urban counties for colorectal cancer, bladder cancer, and leukemia, and lower incidence for liver and breast cancers. Rural residents had higher colorectal cancer mortality and lower liver cancer mortality. Rural residents experienced higher survival from breast and bladder cancers and lower survival from lung, pancreatic, and ovarian cancers, and myeloma. Compared to urban residents, rural residents were less likely to engage in cancer screening and human papillomavirus vaccination. They were more likely to smoke cigarettes and report no leisure time physical activity. Interviews revealed rural cancer needs related to transportation, accessible care, and education.</p> Conclusion <p>The approach that this COE team used to assess its catchment area’s cancer burden may be an informative approach for other cancer centers to understand their own catchment areas. The data collected will inform policies and direct cancer center research and clinical practices to reduce Iowa’s cancer burden.</p>