The CMV Transmission and Immune Tracking (TransmIT) Study aims to enhance understanding of cytomegalovirus (CMV) transmission in early education and care (EEC) settings. This community-engaged, two-stage study employs partnerships with EEC centers, digital platforms, and infrastructure for data collection to facilitate longitudinal virologic and immunologic surveillance in environments with high exposure risk. Stage I focused on establishing key components, including a diverse network of EEC centers, culturally appropriate recruitment methods, a community advisory board, and protocols for participant enrollment and saliva sample collection. Laboratory assays were optimized to measure viral shedding in saliva. The methodologies developed during Stage I will support future investigations into viral shedding patterns, immune responses, and co-infections among children and staff in EEC centers. The study’s framework is designed to be scalable and community-centered, with implications for CMV and other infectious diseases that pose public health challenges.