Purpose: In the US, the COVID-19 pandemic has exposed deeply rooted resistance to public health. This has important consequences for SARS-CoV-2 variant spread and for future uptake of influenza and other vaccines. We examine these phenomena in Missouri, where its low vaccination rates, high levels of uninsured residents, predominance of conservative values, and stark rural-urban divides are intricately connected to public health resistance. The Socio-Ecological model guides our approach. Methods: We use data from the Fall 2020 Midwestern University (MWU—a pseudonym) Study of Seropositivity and Risk for SARS-CoV-2 and COVID-19 which are harmonized with the American Community Survey, Missouri County-Level Study, and the USDA Rural-Urban Continuum Codes to estimate multi-level regression models on the relationship between undergraduate students’ “home” locales and their own COVID-19 and influenza vaccine hesitancy. Findings: The availability of primary care physicians, the prevalence of influenza vaccinations, and location type at the county level, as well as the percentage of residents without health insurance at the zip code level differentially predict COVID-19 and influenza vaccine hesitancy. Conclusions: There is a link between county-level health and geographic characteristics, and individuals’—who were influenced by those counties because that is where their parents live—hesitancy towards vaccines. Identifying feasible, precise, local solutions to reducing vaccine hesitancy could take place if community members and other stakeholders would be open to changes in local-level health policy or practice.