Inequity in preexposure prophylaxis (PrEP) care in the US South and rural communities is likely attributed to Social Determinants of Health and structural issues beyond individuals' control. We describe three approaches to modify PrEP care practice models to make access easier—“normalizing,” “digitalizing,” and “simplifying.” “Normalizing” approaches are defined as practice models where medical providers who have access to PrEP candidates prescribe PrEP routinely (e.g., primary care providers, community pharmacists); these approaches are found to be highly applicable in real-world settings. Telehealth and other dHealth tools are examples of “digitalizing” PrEP, and their use has been increasing rapidly since the COVID-19 pandemic. “Simplifying” PrEP care (e.g., with HIV self-testing, on-demand PrEP) is highlighted in the most recent World Health Organization PrEP guideline. Identifying, implementing, and scaling up these new strategies can allow PrEP candidates to access it, potentially addressing inequities and promoting HIV risk reduction in the US South and rural communities.