Development of drug delivery systems, not the drug discovery, has become more cynosures towards the efficacy of drug against the target cells. Modified hybrid cationic vesicles (HCV) were formulated using soylecithin (SLC), ion pair amphiphile (IPA, hexadecyltrimethylammonium-dodecylsulfate, HTMA+-DS−), bi-tail cationic surfactant dialkyldimethylammonium bromides (DXDABs, bis-C12 to C18) and cholesterol. Piroxicam (Px), a conventional non steroidal anti inflamatory drug (NSAID), with potent yet unexplored anticancer activity, was encapsulated in the hybrid vesicles. Dual impact of DXDABs and Px on SLC/IPA were scrutinized in the form of monolayer, bilayer and solid supported bilayer. Favourable hydrophobic inteaction between SLC/IPA anddihexadecyldimethylammonium bromide (DHDAB) as well as the intercalation of Px molecules between the amphiphiles were noticed through the surface pressure area measuremnts. Vesicles without and with Px were fairly monodisperse with positive zeta potential (Z. P.) and considerably stable upto two months. Size of the vesicles enhanced with Px incorporation. Vesicles maintain spherical morphology as revealed from the electronic microscopic studies. Differential scanning calaorimetry and FTIR studies confirm the location of Px membrane palisade that enhances the extent of hydration by increasing the proportion of H-bonding. Bilayer thickness and the spacing between two adjecent lamellar phase were investigated by combined small angle neutron scattering and small angle X-ray scattering. Atomic force microscopic studies confirm the Px induced fluidization of membrane bilayer. The entrapment efficiency of vesicles to host Px depends on the amount of IPA present in the bilayer. Px hosted cationic vesicles showed less than 2% hemolysis. The drug reigned supreme over human neuroblastoma cell line (SH-SY 5Y) when encapsulated inside the membrane and was non toxic to normal human blood cell lymphocyte (PBMC) as revealed from cytotoxicity assay.