To our knowledge, this is the first report demonstrating the successful sequential integration of radiotherapy and EGFR-TKI therapy in SMARCA4-dNSCLC.<h4>Conclusion</h4>Our experience demonstrates that a proactive, individualized multimodal strategy-integrating radiotherapy for local control and targeted therapy guided by dynamic molecular profiling-can significantly extend survival beyond the historical median of approximately 12 months for SMARCA4-deficient NSCLC. The gene discussed is SMARCA4; the disease is non-small cell lung carcinoma.