This study aimed to assess the implementation of the Brazilian National Program for Genomics and Precision Public Health (GenBR) over its initial five years, identifying key achievements, challenges, and lessons for integrating genomics into public health systems in low- and middle-income countries (LMICs). Established by Ministerial Ordinance GM/MS No. 1,949 on August 4, 2020, GenBR aims to lay the foundation for genomics and precision health within Brazil’s Unified Health System. Its primary goals include advancing science and technology countrywide, fostering the development of a national genomics industry, and conducting proof-ofconcept studies to assess the practical application of precision health in public healthcare. By August 2025, over 250 research projects had been funded in 19 of the country’s 27 federative units, across a range of areas, including oncological, rare, cardiovascular, infectious, neurological, and non-communicable diseases, as well as population genomics and precision health. Financial investments had exceeded BRL 1 billion, funding the sequencing of 67,000 samples. Nine large-scale genomics research projects associated with the Program have contributed to generating whole-genome data from 45,910 individuals. Moreover, four public calls have selected 209 research projects led by science and technology institutions located across all regions of Brazil. GenBR offers key lessons for LMICs seeking to implement genomics in public health, particularly in contexts marked by population diversity, infrastructure asymmetries, and fiscal constraints. Findings highlight the importance of sustained political commitment, inclusive governance, and long-term planning for building national genomic capacity and advancing health equity.