Vibrio parahaemolyticus is a halophilic, Gram-negative bacterium widely distributed in marine and estuarine environments and recognized as a leading cause of seafood-associated gastroenteritis worldwide. In recent decades, its global emergence has been driven by environmental changes, particularly ocean warming, as well as the intensification of aquaculture and the globalization of seafood trade. This narrative review provides a comprehensive overview of the epidemiology, virulence factors, antimicrobial resistance, and One Health dimensions of V. parahaemolyticus. The pathogen’s ability to cause disease in humans is largely determined by key virulence determinants, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and secretion systems that facilitate host colonization and cytotoxicity. From a One Health perspective, V. parahaemolyticus represents a critical interface among environmental, animal, and human health, and also causes severe diseases in aquaculture, including acute hepatopancreatic necrosis disease (AHPND) and translucent postlarval disease (TPD) in shrimp, as well as vibriosis in bivalve mollusks such as oysters, where infection may result in tissue damage and substantial larval and juvenile mortality, with important economic consequences. The increasing emergence of antimicrobial-resistant strains further complicates clinical management and highlights the role of environmental reservoirs and aquaculture practices in the dissemination of resistance. Additionally, climate-driven changes in temperature, salinity, and marine ecosystems are expanding the geographic distribution and seasonal dynamics of this pathogen. Strengthening integrated surveillance systems, improving food safety practices, and promoting interdisciplinary research, including studies of the molecular mechanisms underlying interactions between the epigenome and V. parahaemolyticus, are essential to mitigate the growing risks associated with V. parahaemolyticus. A comprehensive One Health approach is critical to address its evolving impact on global public health and food security.