This comparative analysis explores HIV prevention, PrEP (pre-exposure prophylaxis), and health equity across two critical border regions: San Diego–Tijuana and Brownsville–Matamoros. These binational corridors reflect unique public health dynamics shaped by migration, resource allocation, stigma, and cross-border collaboration. While San Diego and Brownsville benefit from robust U.S. public health infrastructure, their Mexican counterparts often face limitations in consistent access to HIV testing, PrEP availability, and stigma-free services.