Abstract
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains a leading cause of cancer-related mortality globally. The biological heterogeneity of NSCLC challenges early detection, accurate staging, and optimal therapy. Recent advances in artificial intelligence (AI) and machine learning (ML) have enabled the integration of high-dimensional clinical, genomic, and imaging data, transforming cancer care. This narrative review critically examines recent AI/ML applications in NSCLC, emphasizing clinical validation, interpretability, and ethical deployment. We synthesize data from leading studies on imaging, genomics, and multimodal integration, highlighting how deep learning and ensemble methods have begun to outperform traditional diagnostic workflows. Persistent challenges, including dataset diversity, lack of external validation, interpretability, and ethical considerations must be addressed to realize translational impact. We advocate for large-scale, interdisciplinary collaboration to advance AI-powered personalized medicine and improve patient outcomes in NSCLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-026-02821-4.