Uveal melanoma (UM) is an aggressive intraocular cancer that, in 50% of cases, spreads to the patient’s other systems. The exact cause of the increased metastatic rate is still unknown. Methylation and immune response, metastasis, and the expansion of cancer cells are closely related. Additionally, proteins linked to RNA methylation have come to light as possible cancer treatment targets. However, the relationship between methylation-related genes (MRGs) and the tumor microenvironment (TME) is still not understood. The goal of this work was to discover important MRGs and create a signature for UM patients’ prognosis prediction. Using two different data sets, we examined the MRG expression patterns in the transcriptional and genomic regions of 106 UM samples. We discovered a connection between the clinicopathological traits of the patients, their prognosis, the capability of TME cells to infiltrate, and various MRG changes. Following that, we developed an MRGs signature to forecast prognosis, and we evaluated the model’s precision in patients with UM. We grouped the patients into multiple categories based on their clinical traits, looked at the survival rates for various groups within various groupings, and tested their accuracy. Additionally, to increase the practical usability of the MRGs model, we created a very accurate nomogram. TIDE scores were higher in the low-risk group. We go over how MGRs could impact UM’s TME, immunotherapy responsiveness, prognosis, and clinically significant features. We looked for different chemotherapeutic drugs and cutting-edge targeted agents for patients in diverse subgroups in order to better understand MRGs in UM. This helped in the creation of customized therapy to open new doors. We could also further research the prognosis and develop more efficient immunotherapy regimens.