AIMS: Previous studies indicate that MAF BZIP Transcription Factor F (MAFF) facilitates ectopic metastasis and tumor cell migration. While its role in neoplasm progression is recognized, a thorough pan-cancer analysis of MAFF's impact remains pending. MAIN METHODS: MAFF expression across normal and tumor tissues was analyzed using transcriptomic data from Genomic Data Commons (GDC) and UCSC XENA, with protein details from Human Protein Atlas (HPA) and GeneMANIA. Tumor Immune Single-cell Hub (TISCH) and Spatial Transcriptomics Omics DataBase (STOmics DB) identified MAFF expression in the tumor microenvironment (TME). MAFF's prognostic significance and immune-related gene associations were evaluated through univariate Cox regression, TIMER2.0 immune cell infiltration analysis, and Spearman correlation. Critical pathways were identified using Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), while molecular docking explored anticancer agent interactions. KEY FINDINGS: MAFF expression varies across cancers, affecting tumor prognosis, notably in monocytes/macrophages and endothelial cells. Copy number variation (CNV) positively correlates with MAFF expression, while methylation shows inverse correlation. MAFF mutations significantly affect LGG patient prognosis and correlate with immune therapy responses. ESTIMATE and immune profiling linked MAFF to immunosuppression pathways. Molecular docking identified MAFF-targeted drugs, with validated effects on breast cancer and endometrial cancer cell survival and migration in vitro. SIGNIFICANCE: Multi-omics analysis identified MAFF as a potential prognostic marker correlating with tumor immunity and microenvironment, suggesting its value for personalized cancer immunotherapy, particularly in BRCA and UCEC.