Abstract: Gut dysbiosis appears to be a central driver of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD) comorbidity. Under diet, lifestyle, and host genetic constraints, the microbiome shifts toward a metabolite profile marked by lower short-chain fatty acids, an imbalanced bile-acid pool, and accumulation of detrimental microbial products. The resulting loss of barrier integrity facilitates metabolic endotoxemia and sets off hepatic metabolic rewiring with inflammatory amplification. Liver-derived mediators then interact with gut signals to promote trained immunity in the bone marrow and sustain systemic inflammation, contributing to endothelial dysfunction, atherogenesis, and cardiac remodeling. Importantly, impaired cardiac function feeds back on the gut: congestion and hypoperfusion worsen permeability and intensify dysbiosis, creating a vicious cycle. Targeting the gut–liver–heart axis using microbiota modulators or drugs aimed at specific pathways could therefore yield coordinated benefits across organs. Future work should combine multi-omics with longitudinal sampling to derive microbiomebased stratification tools for precision management of MASLD with CVD.