Background: Metastatic melanoma is an aggressive disease with a rapid systemic dissemination. We evaluated the effect of metastatic sites on the utilization immunotherapy and survival outcomes in stage IV melanoma. Methods: The National Cancer Database from 2010-2017 was queried for stage IV melanoma. Those with missing relevant data were excluded. Patients were grouped into five categories based on metastatic sites: lung metastasis only, brain metastasis only, liver metastasis only, bone metastasis only and multiple sites metastasis. Multivariable logistic regression was used to predict use of immunotherapy. Effects of immunotherapy on overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards model. Results: A total 12, 315 were included in the study, among whom 2206 (17.9%) had lung metastasis only, 1,873 (15.2%) had brain metastasis only, 785 (6.4%) had liver metastasis only, 662 (5.4%) had bone metastasis only and 5,983 (48.6%) presented with multiple metastatic sites. Surgery at primary site was performed in 34.3% of patients with bone metastasis (p<0.001), and radiation therapy was delivered to 69.2% patients with brain metastasis (p<0.001). Site of metastatic disease was associated with immunotherapy utilization, with multiple sites (OR = 1.149, p=0.012), and distant lymph nodes (OR=2.867, p<0.001) demonstrating the strongest association, while patients with oligo brain metastasis were less likely to receive immunotherapy (OR = 0.486, p<0.001). Immunotherapy is associated with superior survival among metastatic melanoma patients (HR=0.433, P<0.001). The Kaplan-Meier curves showed the median overall survival among the immunotherapy group was 33.7 months for lung metastasis (vs. 13.4 months without immunotherapy, HR=0.633, p<0.001), 25 months for brain metastasis (vs. 6.7 months without immunotherapy, HR=0.447, P<0.001), 16.8 months for liver metastasis (vs. 4.2 months without immunotherapy, HR=0.449, P<0.001), 18.3 months in bone metastasis (vs. 7.6 months without immunotherapy, HR=0.615, p<0.001) and 12.1 months in multiple metastasis (vs. 3.8 months without immunotherapy, HR=0.338, p<0.001). Conclusions: Utilization of immunotherapy is influenced by location of metastatic disease in stage IV melanoma. Overall survival is improved for patients treated with immunotherapy.