Background: The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) plays an essential role in iron uptake as an iron reductase. Previous studies found that STEAP3 may play crucial roles in tumorigenesis. However, a comprehensive pan‐cancer analysis of the prognosis and immunity of STEAP3 has not yet been reported. Methods: We performed a systematic analysis of the prognosis and immunity of STEAP3 in human pan-cancer. The data analysis and visualization were completed with R and Cytoscape. STEAP3 expression in cell lines and tissues was measured in multiple ways. Functional validation experiments were performed by shRNA knockdown inA498 and 786-O cell lines. Cell proliferation and invasive ability was detected by CCK-8 assay, transwell assay and wound healing assay. Results: In most tumor tissues, STEAP3 expression was remarkably upregulated and correlated with prognosis, particularly in clear cell renal cell carcinoma (ccRCC). Furthermore, STEAP3 expression was closely correlated with immune infiltrates and may induce recruitment and polarization of M2 macrophages in ccRCC. STEAP3 may be valuable for predicting responses to immune-checkpoint blockade (ICB) therapy. In addition, enrichment analysis results indicated that STEAP3 was positively related to immune-related pathways, P53 pathways and epithelial-mesenchymal transition (EMT). Finally, we demonstrated that STEAP3 was highly expressed in ccRCC tissues and might stimulate EMT via the downregulation of CDH1 in vitro in ccRCC. Conclusion: STEAP3 might function as a prognostic biomarker and immunotherapy response predictor in various cancers. Especially in ccRCC, STEAP3 is a new prognostic biomarker and exerts tumor-promoting function via stimulating the invasion and EMT and inducing recruitment and polarization of M2 macrophages.