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Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by acute hypoxemic respiratory failure (AHRF) and diffuse pulmonary inflammation, which can be triggered by diverse intrapulmonary, extrapulmonary, and host-related factors. Over recent decades, basic research and clinical trials have significantly advanced our understanding of ARDS mechanisms, and effective comprehensive critical care interventions, including lung-protective ventilation, prone positioning, and individualized fluid management, have been widely implemented. Nevertheless, ARDS continues to be associated with substantial morbidity and mortality, and its marked clinical and biological heterogeneity remains a major obstacle to effective management and therapeutic translation. This review summarizes current evidence on ARDS epidemiology, etiology, pathophysiology, diagnosis, and clinical management. We also trace the evolution of diagnostic criteria, including the latest global definition, and critically examine disease heterogeneity, recent advances in critical care strategies, emerging therapeutic approaches, barriers to clinical translation, and future research priorities. Particular emphasis is placed on integrating clinical, physiological, and multi-omics data to support biologically and clinically meaningful patient phenotyping grounded in disease mechanisms. Building on this phenotypic stratification, innovative trial designs, including predictive enrichment and adaptive platform trials, may facilitate the development of more individualized, targeted, and dynamically adjusted treatment strategies for ARDS. In summary, establishing a precision medicine framework for ARDS that integrates etiology, mechanistic insights, phenotype-based patient stratification, individualized therapeutic strategies, and long-term management will be essential to address current challenges and improve patient outcomes.