The One Health approach offers an integrative framework to understand infectious threats, environmental factors, antimicrobial resistance (AMR) and how their interactions affect the human–animal–environment interface. This review examines the epidemiology, transmission pathways, and mechanisms of microorganisms of public health importance (bacteria, fungi, parasites, and viruses). It highlights the interconnectedness of ecosystems, where the environment plays a central role in the dissemination of pathogens, driven by climate change, globalization, agricultural intensification, and habitat degradation. AMR is a major concern, driven by the indiscriminate use of pharmaceuticals in human, veterinary, and agricultural settings, horizontal gene transfer through mobile genetic elements, and microbial evolution. The study of different pathogens is of great importance due to their high prevalence in different ecosystems, their virulence, clinical interest, and mortality rates produced. Some of them are ESKAPE bacteria, Candida auris, Plasmodium falciparum, and emerging viruses such as SARS-CoV-2, which present complex transmission dynamics influenced by ecological and health determinants. The review also addresses the effects of climate change on the persistence and geographic spread of pathogens. Successful implementation of the One Health program requires intersectoral policies, integrated surveillance systems, prudent use of antimicrobials and investment in translational science. Coordinating these strategies is essential to limit the spread of pathogens, protect biodiversity, and save global health in the face of the growing threat of infectious diseases.