<p>Lung cancer remains the second most commonly diagnosed cancer and the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC), accounting for approximately 85% of lung cancer cases, is the most prevalent form. Treatment options for NSCLC include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted drug therapies. Among these, immune checkpoint inhibitors targeting PD-1/PD-L1 have demonstrated significant potential, particularly in improving treatment outcomes. However, their clinical efficacy is impeded by challenges such as toxicity, resistance development, and variable patient responses. Emerging evidence highlights the critical role of the gut microbiome as an important modulator of immune responses in NSCLC, particularly in the context of anti-PD-1/PD-L1 therapies. Specific gut microbes, such as <i>Akkermansia muciniphila</i>, have been associated with improved responses to immunotherapy, suggesting that modulation of the gut microbiome may enhance treatment outcomes. This review discusses the current understanding of the influence of gut microbiome on NSCLC and its potential to improve the clinical efficacy of anti-PD-1/PD-L1 therapies. By integrating microbiome-based insights into personalized treatment strategies, we can overcome the limitations of current immunotherapy approaches and optimize patient outcomes. This review aims to serve as a resource for the scientific community by providing insights into how modulation of gut microbiome may enhance treatment outcomes in NSCLC patients receiving anti-PD-1/PD-L1 immunotherapy.</p> Graphical Abstract <p></p>