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, 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. Molecular imaging techniques targeting the tumor immune microenvironment can visualize tumor heterogeneity, offering new advancements in identifying effective biomarkers to assess response. This article reviews the current development in nuclear medicine for targeting biomarkers of tumor immune microenvironment to assess response to immunotherapy.