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By combining isotopically labeled substrates with metabolic flux analysis (MFA), SIRM enables dynamic, quantitative tracking of carbon flux through mitochondrial pathways. This review focuses on three disease contexts where SIRM has provided transformative insights: cancer, neurodegenerative disorders (Alzheimer's and Parkinson's diseases), and metabolic syndrome (type 2 diabetes and non\u2010alcoholic fatty liver disease). Recent applications have delineated reprogramming signatures, identified metabolic dependencies, and elucidated drug mechanisms. SIRM also facilitates therapeutic monitoring and resistance assessment, offering quantitative biomarkers for patient stratification. 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