This research article explores the correlation between vitiligo-like depigmentation and melanoma’s antitumor responses and prolonged patient survival. Comparative analyses were made to identify a vitiligo signature that was able to accurately act as an effective marker towards immune therapy. Deep learning based efficacy prediction systems were used to identify compounds that could cause an immune activation; of the compounds predicted, Fulvestrant, a selective estrogen receptor degrader, was found to enhance the efficacy of therapy in multiple cancers. RNA datasets were observed with regards to the expression of several vitiligo gene signatures, of which Gzmc and Gzmb genes showed statistically significant increase in respondents towards Fulvestrant. Furthermore, the study found that Fulvestrant treatment significantly increased CD4+ and CD8+ T cell infiltration compared to control breast cancer patients, suggesting that those patients would respond better to immunotherapy. As such, vitiligo gene signatures show potential as an immunotherapy biomarker in determining risk in melanoma.