We show here that the anti‐fibrotic drug nintedanib (BIBF1120, Ofev®) improves the response of the BRAFi/MEKi‐targeted therapy in a preclinical model of melanoma and in BRAF‐mutated cell lines by preventing MAPKi‐induced lineage dedifferentiation, ECM reprogramming, and mesenchymal traits. The gene discussed is BRAF; the disease is melanoma.