Diethyl aminoethyl methacrylate (DEAEMA) was polymerized and cross-linked simultaneously with direct atom transfer radical polymerization (ATRP) of the modified TiO2 and ZnO nanoparticles ((CH3CHBrCOZnO)-Zn-@ and (CH3CHBrCOTiO2)-Ti-@). In the other view, the surface of the TiO2 and ZnO nanoparticles were modified and grafted with poly(DEAEMA). During the ATRP of DEAEMA with (CH3CHBrCOZnO)-Zn-@ and (CH3CHBrCOTiO2)-Ti-@ nanoparticles, different ratios of flutamide, as an anti-cancer drug and the case for the simulation, were added to the polymerization matrix. Meanwhile, the polymer nanocomposites (PNCs) were obtained as a delivering system. Then, the different PNCs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry, and electrochemical investigations. In this regards, electrochemical investigations reveled the fact that the developed delivering systems have the drug release rates of 31.0 over 1560 min and 22.8 in 1200 min for the flutamide-loaded PDEAEMA-(CH3CHBrCOTiO2)-Ti-@ and flutamide-loaded PDEAEMA-(CH3CHBrCOZnO)-Zn-@, respectively. Also, according to the TEM images, the synthesized delivering systems based on (CH3CHBrCOTiO2)-Ti-@ shows the bowl-like arrangements, which likely support the obtained electrochemical and high performance liquid chromatography results. Finally, our study shows that the view of the modifying and grafting of TiO2 and ZnO nanoparticles by poly(DEAEMA) confirmed the great success for the introduced simulated drug delivery system than the view of the TiO2 and ZnO, as modifiers for poly(DEAEMA).