Organ transplantation remains the sole definitive treatment for many forms of end-stage organ failure, yet donor organ shortages impose life-threatening delays for thousands of patients worldwide. Mechanical supports and dialysis provide only temporary respite, while lifelong immunosuppression poses additional risks-including infections, malignancies and considerable healthcare costs. Recent innovations hold promise for overcoming these barriers. Artificial intelligence tools increasingly guide organ allocation decisions by integrating clinical, demographic and immunological data. They also refine rejection monitoring, personalize immunosuppressive regimens and facilitate virtual patient simulations. Meanwhile, xenotransplantation has progressed through multi-gene editing of donor pigs and improved immunosuppressive protocols, edging closer to mitigating hyperacute rejection in kidney, heart and liver grafts. In parallel, regenerative medicine approaches-spanning stem cell therapies, three-dimensional organoids and three-dimensional bioprinting-are poised to create patient-specific tissues that reduce rejection and enhance graft longevity. Biomaterials and cell encapsulation further offer localized immunosuppression, potentially streamlining post-transplant care. Yet widespread clinical adoption requires rigorous validation, ethical frameworks and interdisciplinary collaboration. By combining artificial intelligence-guided diagnostics, innovative organ engineering and advanced immunotherapies, transplant medicine can progress toward a future in which organ scarcity is alleviated, patient outcomes are optimized and healthcare systems operate with greater efficiency.