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This collection reviews the pivotal role of metabolic reprogramming and dysregulation across various diseases. It highlights how altered glucose, lipid, and amino acid metabolism, mitochondrial dysfunction, and signaling pathways drive conditions like diabetes, cancer, neurodegenerative, and cardiovascular diseases. Immunometabolism in immune cells, the influence of gut microbiota, redox signaling, epigenetics, and post-translational modifications emerge as crucial regulatory layers. Furthermore, pharmacogenomics emphasizes personalized medicine. Together, these insights identify novel molecular mechanisms and therapeutic targets, moving beyond conventional approaches to address disease pathogenesis effectively.