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Human metapneumovirus (HMPV) is a major respiratory pathogen belonging to the Pneumoviridae family that primarily affects children, the elderly, and immunocompromised individuals. Since its discovery in 2001, HMPV has been recognized as a significant cause of acute respiratory infections (ARIs) worldwide, exhibiting seasonal peaks and recurring outbreaks. In recent years, the virus has shown an unusual resurgence, particularly in the post-COVID-19 era, emphasizing the need for renewed clinical and epidemiological attention. This review provides a comprehensive overview of HMPV, encompassing its epidemiology, virion structure, replication mechanisms, host-pathogen interaction, clinical manifestations, diagnostic strategies, and current therapeutic approaches. Special attention is given to recent epidemiological trends, molecular insights derived from structural studies of viral proteins, and the challenges faced in developing vaccines and antiviral agents. Additionally, the review discusses the potential of plant-derived bioactive compounds as alternative or complementary therapeutic options. By consolidating the latest global data and highlighting existing knowledge gaps, the work aims to facilitate a better understanding of HMPV pathogenesis and guide future research directions for improved surveillance, diagnosis, and management of HMPV infections.