The clinical development of checkpoint inhibitor-based immunotherapy has revolutionized cancer treatment, offering durable responses in patients with melanoma and other malignancies. However, the risk of immune-related adverse events increases with combination therapies. The need for predictive biomarkers to optimize patient benefit, minimize toxicities, and guide combination approaches is迫切的. The primary focus has been on PD-L1 expression, but PD-L1 testing alone is insufficient for patient selection in most malignancies. This review discusses the status of PD-L1 testing and explores emerging data on new biomarker strategies, including tumor-infiltrating lymphocytes, mutational burden, immune gene signatures, and multiplex immunohistochemistry. Future development will integrate multiple approaches to characterize the immune tumor microenvironment effectively.The clinical development of checkpoint inhibitor-based immunotherapy has revolutionized cancer treatment, offering durable responses in patients with melanoma and other malignancies. However, the risk of immune-related adverse events increases with combination therapies. The need for predictive biomarkers to optimize patient benefit, minimize toxicities, and guide combination approaches is迫切的. The primary focus has been on PD-L1 expression, but PD-L1 testing alone is insufficient for patient selection in most malignancies. This review discusses the status of PD-L1 testing and explores emerging data on new biomarker strategies, including tumor-infiltrating lymphocytes, mutational burden, immune gene signatures, and multiplex immunohistochemistry. Future development will integrate multiple approaches to characterize the immune tumor microenvironment effectively.