The objective of the present study was to formulate and optimize exemestane (EXM) encapsulated vitamin E-TPGS-poly-ɛ-caprolactone based polymeric nanoparticles (TPGS-PCLNPs) for enhancing its anticancer efficacy. The 2 factorial design was employed to investigate the combined influence of formulation and process variables on properties of TPGS-PCLNPs, prepared by nanoprecipitation method. The physicochemical characterization revealed the encapsulation of EXM in amorphous form without any interaction inside spherical shaped TPGS-PCLNPs. In vitro cytotoxicity study on MCF-7 breast cancer cells exhibited enhanced cytotoxicity of EXM by encapsulating in TPGS-PCLNPs. The TPGS-PCLNPs can serve as potential delivery vehicle for EXM to improve its therapeutic efficacy.