Objectives: Stage III NSCLC represents one of the most heterogeneous and clinically challenging scenarios in thoracic oncology. The rapid integration of immunotherapy into multimodal treatment strategies has reshaped therapeutic algorithms, particularly for resectable and borderline resectable diseases. However, uncertainty persists regarding optimal staging procedures, resectability assessment, and the integration of surgery, systemic therapy, and radiotherapy. Methods: A multisocietal Delphi consensus was conducted to address key areas of uncertainty in the multidisciplinary management of stage III NSCLC. Experts in thoracic surgery, medical oncology, radiation oncology, interventional pulmonology, and pathology, nominated by four Italian scientific societies, participated in a structured consensus process. Sixty-five statements covering baseline evaluation, local treatment, and integrated therapeutic strategies were rated using a 9-point Likert scale across two Delphi rounds. Results: Consensus was achieved for 62 of 65 statements. Strong agreement supported comprehensive baseline staging, including contrast-enhanced computed tomography, positron emission tomography imaging, brain magnetic resonance imaging, and systematic mediastinal staging with endosonographic techniques. Molecular characterization, including Programmed Death-Ligand 1 expression and testing for EGFR and ALK alterations, was considered essential for treatment selection. Neoadjuvant chemo-immunotherapy was endorsed as the preferred strategy for most patients with resectable stage III NSCLC without actionable driver alterations. Lung-sparing surgical procedures were strongly favored, while pneumonectomy should be reserved for highly selected cases. For unresectable disease, concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. Conclusion: This multidisciplinary consensus provides an updated framework for the contemporary management of stage III NSCLC, emphasizing accurate staging, molecular profiling, and coordinated multidisciplinary decision-making to optimize multimodal treatment strategies.
