This work aimed at formulating paclitaxel (PTX) loaded cell penetrating peptide (CPP) coated Mn doped ZnS nanoparticles (Mn:ZnS NPs) for improved anti-cancer efficacy in vitro and in vivo. The developed PTX loaded Mn:ZnS NPs with different CPPs (PEN, pVEC and R9) showed enhanced anti-cancer effect compared to bare PTX, which has been validated by MTT assay followed by apoptosis assay and DNA fragmentation analysis. The in vivo bio-distribution and anti-cancer efficacy was studied on breast cancer xenograft model showing maximum tumor localization and enhanced therapeutic efficacy with R9 coated Mn:ZnS NPs (R9:Mn:ZnS NPs) and was confirmed by H/E staining. Thus, R9:Mn:ZnS NPs could be an ideal theranostic nano-carrier for PTX with enhanced the rapeutic efficacy toward cancer cells, where penetration and sustainability of therapeutics are essential.