Checkpoint inhibitor‑based immunotherapy has exhibited unprecedented success in the treatment of advanced‑stage cancer in recent years. Several therapeutic antibodies targeting programmed death‑1 (PD‑1) or its ligand (PD‑L1) have received regulatory approvals for the treatment of multiple malignancies, including melanoma, non‑small cell lung cancer, kidney cancer and Hodgkin's lymphoma. However, a substantial proportion of patients still do not benefit from these agents, let alone the risk of immune‑associated toxicities and financial burden. Therefore, it is imperative to identify valid predictive biomarkers which can help optimize the selection of patients. In this review, a mechanism‑based interpretation of tumor PD‑L1 expression and other candidate biomarkers of response to antitumor PD‑1/PD‑L1 blockade was provided, particularly for the tumor microenvironment‑derived ‘immunomes’, and the challenges faced in their clinical use was addressed. Directions for future biomarker development and the potential of combined biomarker strategies were also proposed.