PURPOSE: To investigate the expression and clinical significance of insulin-like growth factor 2 mRNA-binding protein family members (IGF2BPs) in pan-cancer and evaluate their potential as targets for tumor immunotherapy. METHODS: Based on data from the cancer genome atlas (TCGA) database, pan-cancer analysis was conducted to examine the clinical significance of IGF2BPs expression in twenty-two tumors. RESULTS: Differential expression analysis showed high expression of IGF2BPs in most tumor tissues. Survival and mutation analyses suggested that the overexpression of IGF2BPs was associated with poor prognosis and mutation status of certain tumors. Methylation analysis revealed the methylation levels of IGF2BP1/2/3 in certain tumors were intricately linked to their mRNA expression, patient prognosis, and immune cell infiltration. Enrichment analysis indicated that abnormal expression of IGF2BPs was associated with various common tumor-related pathways in different tumors, including AMPK, Hippo, PI3K-Akt, EMT, and p53. In addition, immune correlation analysis revealed that IGF2BPs were closely related to immunotherapy-related indicators (immune cell infiltration, major histocompatibility complex (MHC), immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI)) in some tumors. Drug sensitivity analysis indicated that IGF2BPs were sensitive to some common chemotherapeutic drugs (alvocidib, dasatinib, trametinib, and selumetinib). CONCLUSION: IGF2BPs exhibit significantly high expression in most tumors and are associated with prognosis, pathological stage, mutational status, methylation levels, and the relevant indicators of immunotherapy sensitivity in multiple tumors. Moreover, IGF2BPs may play an oncogenic role by activating common signaling pathways. Therefore, IGF2BPs may be potential prognostic markers for tumor therapy and targets for immunotherapy and drug therapy.