This study provides a comprehensive overview of SARS-CoV-2 genomic surveillance in Central America and the Dominican Republic from February 2020 to January 2023, highlighting the collaborative efforts of the Pan American Health Organization (PAHO), and the Council of Ministers of Health of Central America (COMISCA). A total of 26, 595 sequences from the GISAID database were analyzed, correlating findings with key events reported by participating entities. The genomic analysis reveals significant co-circulation of variants, with notable lineage diversity observed throughout the pandemic. Variants of concern (VOC) like Alpha, Gamma, Delta and Omicron were identified alongside variants of interest (VOI) like Lambda and Mu. The emergence of recombinant lineages further illustrates the ongoing evolution of the virus and its spread across the region, underscoring the interconnectedness of Central America and the Dominican Republic. The collaborative model facilitated broader sequencing coverage, enabling more extensive surveillance than individual countries could achieve alone. Despite the successes of regional collaborations, challenges remain, particularly regarding sequencing capacity in countries impacted by socioeconomic inequalities. Addressing these gaps is essential to enhance public health responses to current and future pandemics.