Abstract: Distant metastases are inevitable in patients with advanced non-small cell lung cancer (NSCLC), and the brain is one of the most common site of metastasis. Patients who suffer brain metastases (BM) may have headaches, blurred vision, hemiplegia, limb numbness, and other symptoms. Quality of life is severely impacted for these patients. Previous studies have shown that prognosis for patients with BM is usually very poor, and natural median survival time is only about 3 months. Traditional treatment strategies for driver-gene negative NSCLC patients with BM include local intervention surgery, radiotherapy, and systemic chemotherapy. New generation targeted drugs can be used for patients with gene mutations such as EGFR, ALK, and ROS1. However, the efficacy of both approaches has not been optimized in patients with BM. Immunotherapy based on immune checkpoint inhibitors (ICIs) has brought new hope to patients with advanced NSCLC. A large number of randomized clinical trials have shown that the application of ICIs on melanoma and NSCLC patients with BM can produce amazing anti-tumor effects compared with chemotherapy. Studies have confirmed that the vasculature in BM is significantly different from normal cerebral vasculature. BM also establish a unique tumor microenvironment, and unique immune cell components and functions. The characteristics of immune cells infiltrating metastases are different from those infiltrating primary lesions. In addition, several retrospective studies have found that either immune-monotherapy or combined immunotherapy is effective in lung cancer patients with BM. Research into predictive biomarkers for assessing the efficacy of immunotherapy is hampered by the difficulty of obtaining brain tissue samples. In addition to programmed cell death ligand-1 (PD-L1) expression in tumor cells, tumor mutation burden (TMB) may be a potential biomarker to predict the efficacy of immunotherapy. This review focuses on tumor microenvironment of NSCLC metastases, and surveys progress in ICI therapies, to provide a reference for the treatment of NSCLC patients with BM.