In this single-center retrospective case series, we conducted a comprehensive analysis of the efficacy and safety of regorafenib combined with BRAF/MEK inhibitors in twenty-two patients with stage IV-M1d, BRAF- or NRAS-mutant melanoma who were progressive after standard-of-care treatment with ICB and BRAF/MEK inhibitors (in case of BRAFV600-mutation). Here, NRAS is linked to melanoma.