Immunotherapy is currently the most promising clinical treatment for lung cancer, not only revolutionizing second-line therapy but now also approved for first-line treatment. However, its clinical efficiency is not high and not all patients benefit from it. Thus, finding the best combination strategy to expand anti-PD-1/PD-L1-based immunotherapy is now a hot research topic. The conventional use of chemotherapeutic drugs and targeted drugs inevitably leads to resistance, toxic side effects and other problems. Recent research, however, suggests that by adjusting the dosage of drugs and blocking the activation of mutational mechanisms that depend on acquired resistance, it is possible to reduce toxic side effects, activate immune cells, and reshape the immune microenvironment of lung cancer. Here, we discuss the effects of different chemotherapeutic drugs and targeted drugs on the immune microenvironment. We explore the effects of adjusting the dosing sequence and timing, and the mechanisms of such responses, and show how the effectiveness and reliability of combined immunotherapy provide improved treatment outcomes.Copyright © 2023 Wang, Du, Jiang, Chen and Wang.