With increasing understanding of tumor immune tolerance mechanisms, a series of immune checkpoint molecules have been identified. Immune checkpoint blockade (ICB) therapy, which was developed based on these discoveries, has emerged as a promising strategy for the clinical treatment of non-small cell lung cancer (NSCLC), and has shown notable therapeutic benefits. However, the limited response rate remains a major barrier to further improving ICB efficacy and poses a significant challenge to the clinical management of NSCLC. This review summarizes recent advances in clinical immunotherapy for NSCLC and discusses future prospects in the field.A systematic literature search was performed using the official websites of organizations and databases, including PubMed, the United States (US) Food and Drug Administration (FDA), China's National Medical Products Administration (NMPA), the National Cancer Institute (NCI), the National Comprehensive Cancer Network (NCCN), the Chinese Society of Clinical Oncology (CSCO), the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) The inclusion criteria were: (I) English-language articles published between 2004 and 2025; and (II) clinical studies specifically addressing immune checkpoint inhibitor (ICI) therapy in NSCLC populations.Researchers have explored various approaches from drug development and treatment response evaluation to combination strategies, and have made substantial progress in enhancing the effectiveness of ICB therapy.ICB therapy for NSCLC has evolved from monotherapy to multimodal combination approaches, and significant breakthroughs have been achieved; however, three major challenges persist; that is, acquired drug resistance, a lack of reliable biomarkers, and the suboptimal management of special patient populations. To address these issues, future research should focus on: (I) elucidating resistance mechanisms through multi-omics approaches; (II) developing novel biomarkers and next-generation targeted agents; and (III) refining combination therapy regimens. These coordinated efforts will ultimately enable personalized precision immunotherapy tailored to individual patients' molecular profiles and clinical characteristics.Copyright © 2025 AME Publishing Company. All rights reserved.