Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by activating anti-cancer immunity through blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, ICIs have limitations, including low response rates, severe side effects, and high costs. Therefore, identifying biomarkers to predict patient response and prevent adverse events is crucial. This review discusses established predictive biomarkers (PD-L1 expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers under investigation, such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. The review highlights the challenges and future prospects of these biomarkers, emphasizing the need for further research and standardization to optimize patient stratification and improve the efficiency of ICIs.Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by activating anti-cancer immunity through blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, ICIs have limitations, including low response rates, severe side effects, and high costs. Therefore, identifying biomarkers to predict patient response and prevent adverse events is crucial. This review discusses established predictive biomarkers (PD-L1 expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers under investigation, such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. The review highlights the challenges and future prospects of these biomarkers, emphasizing the need for further research and standardization to optimize patient stratification and improve the efficiency of ICIs.