Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median follow-up was 31 months (6–108 months). The median PFS1 was 6 months (1–44 months). Second-line systemic treatment was applied in 27 patients (52%). The median PFS2 was 2 months (0–27 months), and the median OS was 31 months (6–108 months). Among the analyzed risk factors, only the presence of the BRAF mutation was statistically significant for disease recurrence after surgery. In patients undergoing anti-BRAF/MEK therapy, the median PFS1 was 7 months, and in patients undergoing mono-immunotherapy, 4 months. The 12- and 24-month PFS1 rates in the group treated with BRAF inhibitors were 29 and 7%, respectively, and in patients treated with mono-immunotherapy 13 and 0%, respectively (Z = 1.998, p = 0.04). The type of treatment used had no effect on OS (Z = 0.237, p > 0.05). Conclusion: Patients with the V600 mutation should be closely monitored. In the event of disease recurrence, treatment with BRAF/MEK inhibitors should be considered. The type of treatment used has no effect on OS.