AIM: To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma (UVM) patients. METHODS: Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas (TCGA)-UVM cohort and an external Gene Expression Omnibus (GEO) microarray dataset (GSE73652; 8 non-metastatic vs 5 metastatic cases) were analyzed to identify differentially expressed genes (DEGs). Functional enrichment, protein-protein interaction (PPI) network construction, and survival analyses identified seven metastasis- and prognosis-related genes. Their expression was further examined using public single-cell RNA-seq data (GSE139829; 11 tumors). Experimental validation was performed in UVM cell lines (92.1, OMM1, MEL270) and adult retinal pigment epithelial (ARPE-19) cells using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to confirm transcriptomic trends. A LASSO Cox model was applied to construct a metastasis-related risk Score signature. Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE. Somatic mutation and copy number variation (CNV) profiles were also examined. RESULTS: Seven key genes (UBE2T, KIF20A, DLGAP5, KLC3, TPX2, UBE2C, AURKA) were significantly associated with overall survival and used to construct a metastasis-related riskScore signature, which effectively stratified patients into high- and low-risk groups and served as an independent prognostic factor. qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells, which were largely consistent with the transcriptomic findings. The high-risk group exhibited reduced immune infiltration and stromal activity. Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential. Mutation and CNV analyses further supported the relevance of these genes to UVM progression. CONCLUSION: This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM. The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations, and may offer guidance for future mechanistic studies and therapeutic exploration.