Nontuberculous mycobacteria (NTM) are environmental opportunistic pathogens with increasing clinical relevance worldwide. Among them, the Mycobacterium avium complex (MAC), comprising species such as M. avium, M. intracellulare, and M. chimaera, is responsible for the majority of human NTM diseases. MAC causes chronic pulmonary disease and disseminated infections, particularly in immunocompromised individuals, although infections in immunocompetent hosts are increasingly reported. Despite advances in molecular diagnostics, accurate species- and subspecies-level identification remains challenging due to high genetic diversity and biased genomic databases. This limitation hampers the understanding of transmission dynamics, antimicrobial resistance patterns, and epidemiological trends. In recent years, whole-genome sequencing (WGS) has emerged as a key tool for high-resolution typing, enabling improved phylogenetic analysis, outbreak investigation, and resistance prediction. This review summarizes current knowledge on MAC taxonomy, clinical manifestations, antimicrobial resistance mechanisms, and ecological distribution, with a particular focus on the role of genomic surveillance. We highlight the need for integrated genomic frameworks to support early detection, accurate classification, and effective public health surveillance of MAC infections globally in a One Health perspective.