OVERALL: ABSTRACT Since achieving NCI designation in 2018, the Stephenson Cancer Center (SCC) at the University of Oklahoma has continued to grow and mature as an organization. The SCC’s vision to eliminate cancer in Oklahoma and beyond is advanced through its mission to provide patient-centered, research-driven, multidisciplinary cancer care to all Oklahomans. As Oklahoma’s only NCI-designated cancer center, the SCC serves a statewide catchment area that presents unique challenges with social determinants of health and high disparities in cancer incidence and mortality, especially for the state’s American Indian (AI), Black/African American, and rural populations. The SCC has the ability to be impactful in its catchment area and nationally due to strategically targeted recruitments and investments that have leveraged key differentiating factors: 1) the SCC continues to invest in creating and sustaining health and research partnerships with AI tribal partners throughout Oklahoma and currently has 22 NIH funded projects addressing AI cancer disparities; 2) the SCC continues to be a national leader in the NCI/NCTN and has established a statewide network of affiliate sites to ensure access to NCI-sponsored clinical trials throughout its catchment area; 3) the SCC has developed strong team-based research across all of its programs with national leadership in gynecologic, colon, and pancreatic cancers, cancer prevention, cancer therapeutics, gero-oncology, and tobacco control; and 4) the SCC is building upon its national leadership in mobile health technologies to address the burden on cancer in rural and vulnerable populations. Multiple NCI CCSG metrics emphasize the growth and maturation of the SCC during the reporting period (2017-21). SCC membership increased from 83 to 120 (45%), with 31 of these new members being externally recruited to add expertise to programs. Annual, peer-reviewed research funding (DC) grew 61% ($14.28M $22.97M) and total annual research funding grew 42% ($30.13M $43.09M). The overall five-year number of scientific publications has increased by 54% since the last reporting period (945 1,454), with 16% having an impact factor ≥10 (up from 7%). Team science has been emphasized resulting in 139 collaborative grants (36% increase) and a 17% inter-programmatic publication rate (up from 4%) over the prior reporting period. The number of annual active interventional IITs has doubled from 20 to 40 over the past five years, with annual accruals to interventional IITs increasing from 661 (2017) to 927 (2021) – a 40% increase. This degree of impactful growth has been possible due to the infrastructure made available through the CCSG and has positioned the SCC for a successful renewal as a NCI-designated cancer center.