BACKGROUND AND OBJECTIVE: The gut microbiome has emerged as an important gateway to improving therapeutic outcomes in lung cancer, especially for immunotherapy. Our objective is to review the impact of the bidirectional relationship between the gut microbiome, lung cancer, and the immune system, and to identify areas of future research. METHODS: We conducted a search on PubMed, EMBASE, and ClinicalTrials.gov using the search terms non-small cell lung cancer (NSCLC), gut microbiome, and microbiota until July 11, 2022. The authors screened resulting studies independently. Results were synthesized and presented descriptively. KEY CONTENT AND FINDINGS: Sixty original published studies were identified from PubMed (n=24) and EMBASE (n=36), respectively. Twenty-five ongoing clinical studies were identified on ClinicalTrials.gov. Gut microbiota has been shown to influence tumorigenesis and modulate tumor immunity via local and neurohormonal mechanisms depending on the microbiome ecosystem that populates the gastrointestinal tract. Probiotics, antibiotics, and proton pump inhibitors (PPIs), amongst other medications, can impact gut microbiome health, leading either to improved or worsened therapeutic outcomes with immunotherapy. Most clinical studies assess the impact of the gut microbiome, but emerging data suggest microbiome composition in other host sites may be important. CONCLUSIONS: A strong relationship exists between gut microbiome, oncogenesis, and anticancer immunity. Although the underlying mechanisms are poorly understood, immunotherapy outcomes seem to depend on host-related factors such as gut microbiome alpha diversity, relative abundance of microbial genera/taxa, and extrinsic factors such as prior or concurrent exposure to probiotics, antibiotics, and other microbiome-modifying drugs.