BACKGROUND: Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi + nivo), have shown efficacy in metastatic cutaneous melanoma, their success in metastatic UM (MUM) remains limited. This study evaluates toxicity and outcomes of ipi + nivo in the largest, multicenter MUM cohort. METHODS: We analyzed 131 MUM patients treated with ipi + nivo from 2016 to 2024 across 5 international centers. Rates of toxicity, response, and survival outcomes were assessed. RESULTS: Among 131 patients, 37.4% of patients received 4 cycles of ipi + nivo. The most common reason for ipi + nivo discontinuation (31.3%) was toxicity. Of all treated patients, 80.2% experienced immune-related adverse events (irAEs). The overall response rate (ORR) was 16.4%, and the disease control rate (DCR) was 43.4%. Progression-free survival (PFS) was three months, and the median overall survival (OS) was 18 months. Patients receiving ipi + nivo as second-line therapy had lower ORR compared to patients who received ipi + nivo as first-line therapy (P = .04). Patients with exclusively extrahepatic metastases had a better ORR and OS compared to those with hepatic or mixed metastases (P = .02, P = .02, respectively). 20.6% of patients developed eosinophilia during treatment, which was associated with improved median OS (24 months vs 15 months, P = .02). CONCLUSIONS: Ipi + nivo shows moderate efficacy and clinically relevant toxicities in patients with MUM. Eosinophilia is a potential prognostic biomarker, that merits further investigation.