Immunotherapy has recently become an important treatment modality, especially for non-small cell lung cancer (NSCLC) and melanoma patients. Several large-scale phase III trials of first-line treatments for metastatic NSCLC have documented prolonged patient survival, including progression-free survival and overall survival for immune checkpoint inhibitors (ICIs) used alone or in combination with chemotherapy. However, a significant proportion of patients experienced disease progression shortly after starting single-agent ICI treatment even after biomarker selection, such as programmed cell death-ligand 1 and tumor mutation burden. The present review was performed to identify ways to enhance ICI efficacy in the first-line treatment of metastatic NSCLC patients. At least four effective ways of combination treatment modalities are currently available, namely, immune therapy in combination with radiotherapy, chemotherapy, antiangiogenesis, or other immunotherapeutic agents.