Sex hormones profoundly influence immune homeostasis, yet their role in regulating tissue-resident memory T cells (TRM) at barrier sites remains poorly understood. We employed publicly available bulk RNA-seq, single-cell RNA-seq, and TCGA database melanoma data to investigate sex-related differences of TRM cells in healthy human skin and melanoma. Our study revealed increased frequencies of cytotoxic TNF+IFNγ+CD49a+ TRM cells in healthy female skin and melanoma skin, and the CD49a+ gene signature correlated with improved survival in female melanoma patients.