Bcl-2 protein plays an integral role in hijacking apoptosis and triggering chemoresistance in triple negative breast cancer (TNBC). The present study explored the therapeutic efficacy of Bcl-2 inhibitor i.e., venetoclax (VTX) loaded HP-β-CD NPs (VTX/HP-β-CD NPs) against TNBC. VTX/HP-β-CD NPs were prepared using nanoprecipitation method. The prepared nanoparticles had optimal size (∼217 ± 4.32 nm), narrow PDI (∼0.23 ± 0.01), higher drug loading (∼15.7 ± 1.94 %) and % entrapment efficiency (∼78.5 ± 1.09 %). Morphology assessment revealed a spherical shape. In-vitro release studies displayed sustained release for up to 72h. Moreover, VTX/HP-β-CD NPs exhibited higher cellular uptake, cytotoxicity, and apoptosis index than free drug. Furthermore, the IC