In the last decade, research on acute respiratory distress syndrome (ARDS) has made considerable progress. However, ARDS remains a leading cause of mortality in the intensive care unit. ARDS presents distinct subphenotypes with different clinical and biological features. The pathophysiologic mechanisms of ARDS may contribute to the biological variability and partially explain why some pharmacologic therapies for ARDS have failed to improve patient outcomes. Therefore, identifying ARDS variability and heterogeneity might be a key strategy for finding effective treatments. Research involving studies on biomarkers and genomic, metabolomic, and proteomic technologies is increasing. These new approaches, which are dedicated to the identification and quantitative analysis of components from biological matrixes, may help differentiate between different types of damage and predict clinical outcome and risk. Omics technologies offer a new opportunity for the development of diagnostic tools and personalized therapy in ARDS. This narrative review assesses recent evidence regarding genomics, proteomics, and metabolomics in ARDS research.