Immune checkpoint inhibitors (ICIs) were promising medical treatments for advanced or metastatic non-small cell lung cancer (NSCLC), while the financial toxicity could not be neglected due to the high cost which might impair the prognosis and quality of life. Thus, we compared the cost-effectiveness analyses to identify the potential financial toxicity of metastatic NSCLC received ICIs.A systematic literature search was performed for the published economic evaluation of ICIs in the Medline and Web of Science databases between January 2015 and September 2021. Only the studies conducting the cost-effectiveness analysis, including total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), were included in our research. We compared the economic outcomes between the immunotherapy group and chemotherapy group and stratified by the programmed death receptor-1 ligand (PD-L1) expression. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist would be employed to check the quality of included papers.A total of 25 studies and 30 cost-effectiveness analyses were included, in which 22 (73.3%) were on Pembrolizumab, eight (26.7%) on Atezolizumab, and 17 (56.7%) on the American payer perspective. In total, the ICER was lower than the willingness to pay (WTP) in 43% of the included analyses. The ICER of Pembrolizumab was lower than that of Atezolizumab (P = 0.049), and it was comparable between ICER and WTP either for Pembrolizumab (P = 0.533) or Atezolizumab (P = 0.056). The economic outcomes were all comparable as stratified by the PD-L1 expression.Immunotherapy could bring financial toxicity, and financial toxicity assessment during clinical decision would weaken the potential impact in the whole course of immunotherapy.© 2025 Huang et al.