Liposomes, polymeric, lipid and inorganic nanoparticles have dominated and proved their clinical effectiveness as a therapeutic or diagnostic agent in oncology research. Being new in concept, PLH nanoparticles witnessed superior performance due to the smart engineering of lipid and polyer counter part by overcoming the limitations of well-established nanocarriers. Notably, PLH nanostructures offered a versatile and multifunctional physicochemical characteristics with enhanced biological effect over other nanocarriers. PLH nanoconstructs is still a budding research area, however its industrial utility beyond laboratory especially during scale up is successful attempted. Preliminary research till date mainly in vitro confirms superior functionalities of PLH than counterpart non-hybrids and lipoplexes or polyplexes.