Symptomatic irreversible pulpitis and apical periodontitis in mature permanent teeth present challenges in their management. Traditional treatment approaches, such as root canal therapy or tooth extraction, may compromise tooth structure and oral function. This review article explores the combination of non-surgical endodontic treatment and vital pulp therapy as an alternative approach for these conditions. The purpose is to examine this combined approach's effectiveness, benefits, challenges, and limitations. The objectives include reviewing the literature, evaluating clinical outcomes, discussing potential benefits, and providing recommendations for clinical practice. The combination approach aims to preserve tooth structure, promote healing, and reduce postoperative complications. The article discusses the rationale for combining the two techniques, presents evidence supporting their efficacy, and outlines the techniques and protocols involved. Clinical outcomes, case studies, potential challenges, and comparative analysis with traditional approaches are also explored. Future directions and research recommendations highlight areas for further investigation, innovations, and the development of clinical guidelines. In conclusion, the combination of non-surgical endodontic treatment and vital pulp therapy offers a valuable strategy for managing mature permanent mandibular molars with symptomatic irreversible pulpitis and apical periodontitis. Further research and advancements are needed to refine the treatment protocol and expand the evidence base, and clinicians should stay updated to provide optimal care and improve patient outcomes.