Aim: Melanoma brain metastases (MBM) are associated with a dismal prognosis. Few clinical trials evaluated the impact of immunotherapy (IT) and targeted therapy (TT) alone or in combination with surgery and radiotherapy in this population. Patients & methods: Retrospective analysis of data from 163 patients diagnosed with MBM between January 2014 and December 2016. Prognostic factors of overall survival were analyzed using Kaplan–Meier survival curves, classification and regression tree and multivariate Cox regression analysis. Results: The median follow-up was 25 months; median overall survival (mOS) for all patients was 7 months. For patients receiving IT, the mOS was 13 months and 7 months for patients receiving TT or chemotherapy (CT). The mOS for patients treated with surgery/radiosurgery in combination with IT, TT and CT was 25, 14 and 11 months, respectively. Conclusion: New systemic therapies, especially IT, improve mOS in patients with MBM, particularly when combined with surgery/radiosurgery upfront.