Objective: The current study’s objective is to assess the transfersomal gel, administration of tamoxifen citrate transdermally for DEPARTMENT OF Expenditure (DOE) Approach. Materials and Methods: Supramolecular clusters with extreme flexibility, known as transferosomes can penetrate untouched animal skin. The formulations were designed by Box-Behnken design (BBD). The ex-vivo skin permeation study of tamoxifen citrate-loaded transferosomal gel was compared with commercial gel and blank drug solution. A total of 100 mg of the maximal drug release (94.32%) from the tamoxifen citrate optimized transferosome formulation demonstrated excellent results. Conclusion: According to this study, the comparatively stable transferosomes represent a promising long-term administration strategy for tamoxifen citrate. According to this study, transdermal drug delivery of skin cancer could be treated by employing transferosomes containing the tamoxifen citrate.