Abstract: Cancer is the one of the leading causes of death. The advent of immunotherapy has significantly changed the clinical management of various tumors. However, due to the heterogeneity of the tumor immune microenvironment (TIME), long-term and sustained control of tumor progression occurs only in a small subset of patients who receive immunotherapy. Currently, the biomarkers and diagnostic methods used to assess patient′s response to immunotherapy have their undeniable limitations. Targeted molecular imaging technologies for the TIME in the field of evaluating valid biomarkers for immunotherapy response by visualizing tumor heterogeneity have achieved new advancements. The authors reviewed the current development status of biomarkers targeting the TIME in nuclear medicine regarding the evaluation of immunotherapy efficacy.