Purpose of Review <p>This review reframes enteral nutrition in critically ill patients as a targeted therapy rather than simple support. It asks whether Mediterranean-style, bioactive-rich formulas containing omega-3 fatty acids, polyphenols, and glutamine can modulate key pathways in sepsis, endothelial dysfunction, and fibrotic remodeling, and whether ICU feeding should be personalized by disease severity, immune profile, and genetic factors.</p> Recent Findings <p>Recent evidence shows these bioactive agents have potent anti-inflammatory, antioxidant, and nutrigenomic effects. They influence cytokine signaling, oxidative stress, and endothelial-to-mesenchymal transition, offering molecular targets for attenuating organ injury.</p> Summary <p>Personalized, metabolism-guided enteral nutrition enriched with Mediterranean bioactive foods may improve tolerance, reduce organ dysfunction, and enhance recovery by directly modulating pathological gene programs. Integrating nutrigenomics into ICU care could transform feeding practices. The review calls for clinical trials to validate these approaches and establish evidence-based guidelines linking diet composition to genetic responses and patient outcomes.</p>