Purpose of Review <p>The Fontan procedure, a palliative surgery for single-ventricle congenital heart disease, often leads to multisystem complications. Elevated bile acids and reduced vitamin D3 levels, frequently observed in this population, may share a harmful bidirectional relationship. This review examines their interplay and therapeutic relevance.</p> Recent Findings <p>Fontan-associated liver disease and potential gut dysbiosis contribute to altered bile acid metabolism, with elevated circulating secondary bile acids impairing cardiovascular, hepatic, musculoskeletal, and immune functions. Recent evidence suggests that bile acid accumulation hinders vitamin D absorption and metabolism. In turn, vitamin D deficiency exacerbates systemic inflammation and fibrosis while reducing bile acid detoxification via diminished vitamin D receptor signaling.</p> Summary <p>The dysregulation of bile acid and vitamin D pathways may create a vicious cycle driving Fontan-associated multisystem dysfunction. Interventions targeting this axis—such as vitamin D supplementation and bile acid modulation—may offer novel strategies to mitigate organ injury and improve long-term outcomes in this high-risk population.</p>