During the COVID-19 pandemic, the CDC Foundation collaborated with implementing partners in Zambia and Tanzania to address challenges related to vaccination access and hesitancy through strategic partnership, technical assistance, and community engagement. These efforts were successful in fostering collaborations among community partners and health authorities and actively engaging the ministries of health. This article describes 2 case studies from Zambia and Tanzania involving different strategies to build health system capacity through projects that improved vaccination access and reduced hesitancy. Such projects illustrate how efforts that strengthen public health and healthcare systems have further positive implications for building localized response systems through context-tailored approaches and building capacity of local healthcare workers. The case studies are examples of public health emergency response projects that successfully increased vaccination access and reduced hesitancy in local communities by rapidly implementing projects to strengthen health system capacity and resilience.