Background IQGAP3 has important function in cancer progression and has become a potential therapeutic target as a transmembrane protein. But its role in tumor immunity and pan-cancer was not systematically investigated. This study evaluated the potential role of IQGAP3 and clinical significance in pan-cancer through combined multiomics analysis. Methods From Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, transcriptomic datasets were first obtained, and from Gene Expression Omnibus (GEO), expression profiling microarray data were acquired and integrated to systematically assess the expression differences and prognostic relevance of IQGAP3 in pancreatic cancer. Immunohistochemical data were obtained from Human Protein Atlas (HPA) to assess IQGAP3 protein expression differences, and exome data from TCGA were used to analyze IQGAP3 expression in relation to tumor mutational burden (TMB), microsatellite instability (MSI), and mutation. Additionally, we also analyzed the relationship between IQGAP3 expression and immune checkpoints, mismatch repair (MMR), and IQGAP3 relationship with methylation and copy number variation based on expression profiles. Results Microsatellite instability (MSI), immune checkpoints, mismatch repair (MMR), and tumor mutational burden (TMB) all closely interacted with IQGAP3 mRNA. In addition, detailed relationships between the immune microenvironment and IQGAP3 mRNA as well as immune cell CD4+ Th2 and myeloid-derived suppressor cells (MDSCs) were determined. Mechanistically, IQGAP3 was involved in cytoskeleton formation, T cell receptor signaling pathways, DNA damage, cell cycle, P53 pathway, Fc gamma R-mediated phagocytosis, and apoptosis. Conclusion IQGAP3 could serve as an effective prognostic biomarker for pan-cancer immune-related therapy.