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The ageing of the cirrhotic population, together with the epidemiological shift toward metabolic dysfunction-associated steatohepatitis, is redefining the profile of patients referred for transjugular intrahepatic portosystemic shunt (TIPS). Although TIPS remains a cornerstone in the management of complications of portal hypertension, its abrupt hemodynamic and metabolic effects challenge the physiological reserve of multiple organ systems. Age-related cardiovascular remodeling, cirrhotic cardiomyopathy, impaired renal function and autoregulation, and reduced neurocognitive reserve interact with the hyperdynamic circulatory state of cirrhosis increasing the susceptibility to heart failure, acute kidney injury (AKI), and hepatic encephalopathy following TIPS. This vulnerability is further amplified by metabolic comorbidities, obesity, sarcopenia, frailty, and age-related alterations of the gut microbiota and gut-liver axis, which collectively promote systemic inflammation, immune dysregulation, endothelial dysfunction, and reduced metabolic adaptability. Rather than independently, these factors shape an interconnected heart-liver-kidney-brain network in which dysfunction in one domain may rapidly propagate to others. This review summarizes how ageing influences the cardiovascular, renal, neurological, and metabolic response to TIPS, critically appraises current strategies for pre-procedural risk assessment, and discusses approaches to improve patient selection and peri-procedural management. Because chronological age alone inadequately reflects procedural risk and clinical outcomes, TIPS evaluation should incorporate a structured assessment of biological ageing, including cardiovascular and renal reserve, neurocognitive vulnerability, sarcopenia, frailty, body-composition phenotype, and metabolic burden. Integrating these domains into pre-procedural assessment may improve patient selection, inform shunt sizing, and ultimately optimize outcomes in this rapidly evolving patient population.