Orofacial defects caused by congenital anomalies, trauma, or surgical procedures present complex challenges that affect physical function and psychological well-being. Maxillofacial rehabilitation, incorporating surgery, endodontics, orthodontics, and implants, aims to restore form, function, and aesthetics. This review evaluates innovative multidisciplinary strategies for orofacial defect management. A narrative review was conducted using PubMed and Google Scholar databases. Search terms included "management of orofacial defects," "maxillofacial surgery," "endodontics in complex cases," "orthodontics in facial surgery," and "dental implants." Articles published between 2014 and 2024 were reviewed, focusing on human studies demonstrating integrated treatment strategies. The interdisciplinary approach to managing orofacial defects, integrating maxillofacial surgery, endodontics, orthodontics, and implants, has demonstrated significant improvements in both functional and aesthetic outcomes. Combined surgical techniques, such as the use of iliac and fibula grafts, offer enhanced graft success through improved vascularization. Technological advancements in endodontics, including CBCT and regenerative procedures, optimize treatment precision. Orthodontic innovations, like clear aligners and mini-implants, enhance patient comfort and treatment efficiency, while digital implant planning reduces complications. The incorporation of growth factors, bioactive materials, and AI further boosts clinical success in treating complex orofacial defects.