AIM: To explore the relationship between matrix metalloproteinases (MMPs) expression levels in the tumor and the prognosis of uveal melanoma (UM) and to construct prognostic prediction models. METHODS: Transcriptome sequencing data from 17 normal choroid tissues and 53 UM tumor tissues were collected. Based on the differential gene expression levels and their function, MMPs family was selected for establishing risk-score system and prognostic prediction model with machine learning. Tumor microenvironment (TME) analysis was also applied for the impact of immune cell infiltration on prognosis of the disease. RESULTS: Eight MMPs were significantly different expression levels between normal and the tumor tissues. MMP-2 and MMP-28 were selected to construct a risk-score system and divided patients accordingly into high- and low-risk groups. The prediction model based on the risk-score achieved an accuracy of approximately 80% at 1-, 3-, and 5-year after diagnosis. Besides, a Nomogram prognostic prediction model which based on risk-score and pathological type (independent prognostic factors after Cox regression analysis) demonstrated good consistency between the predicted outcomes at 1-, 3-, and 5-year after diagnosis and the actual prognosis of patients. TME analysis revealed that the high-risk group exhibited higher immune and stromal scores and increased infiltration of tumor-associated macrophages (TAMs) and regulatory T cells compared to the low-risk group. CONCLUSION: Based on MMP-2 and MMP-28 expression levels, our prediction model demonstrates accurate long-term prognosis prediction for UM patients. The aggregation of TAMs and regulatory T cells in the TME of UM may be associated with an unfavorable prognosis.