The development of a PEG-decorated lipid-polymer hybrid system camouflaged with natural and synthetic chemotherapeutic moieties is an influential approach melding the biomimetic properties of long-circulating vesicles to utilize different mechanisms to dwindle the tumor growth. Therefore, a safe and efficient lipid-coated nano-particulate system (LCNPs) was proposed to investigate the in-vitro, ex-vivo and in-vivo demeanors of such amalgamation.Docetaxel loaded PLGA nanoparticles (DTX-NPs) were prepared by solvent evaporation while curcumin liposomes were mapped out using the film hydration method. Physicochemical characterizations were executed in terms of size, surface morphology, differential scanning calorimetry (DSC) and fourier-transform infrared spectroscopy (FTIR). In-vitro cytotoxicity was effectuated using MCF-7 cell line. Hemolysis, erythrocyte aggregation and acute in-vivo toxicity were carried out to establish the biocompatibility. The hydrodynamic diameters of samples were in the nano-range and corresponded to the findings of scanning electron microscopy (SEM) and atomic force microscopy (AFM). The absence of distinctive peaks of DTX-NPs in FTIR and DSC analysis of LCNPs depicts the shielding of the lipid bilayer over the nanoparticle. Cytotoxicity induced by the LCNPs represented the efficient delivery of cargo to the tumor cells. LCNPs also exhibited the least toxicity under ex-vivo and in-vivo circumstances compared to free drugs. Additionally, histological studies showed no evidence of substantial necrosis. Additionally, histological studies showed no evidence of notable necrosis.