Leukocyte immunoglobulin-like receptor B2 (LILRB2) functions as an immunosuppressive receptor that has a prominent role in immune regulation. The expression of LILRB2 is higher in a variety of solid malignant tumors compared with that in corresponding normal tissues. LILRB2 can be expressed in tumor cells and tumor stromal cells within the tumor microenvironment. Upregulation of LILRB2 in tumors is significantly associated with a poorer tumor phenotype, increased tolerance to certain therapeutic drugs, tumor immune escape and shorter patient overall survival time. Therefore, LILRB2 can be utilized as a novel biomarker to predict the prognosis of patients with solid malignant tumors, and targeting LILRB2 may be an effective strategy for targeted cancer therapy. The present review provides a general overview of the role and mechanisms of LILRB2 in the microenvironment of solid tumors, and emphasizes the significance of targeting LILRB2 as a promising approach for tumor-specific therapy.