The aim of this study was to investigate how the oxidation state of copper (Cu(I) vs Cu(II)), the nature of the interface (solid/aqueous vs solid/air), positional isomerism, and incubation time affect the functionalization of the surface of copper oxide nanostructures by [(butylamino)(pyridine)methyl]phenylphosphinic acid (PyPA). For this purpose, 2-, 3-, and 4-isomers of PyPA and the nanostructures were synthesized. The nanostructure were characterized by UV-visible spectroscopy (UV-vis), scanning electron microscopy (SEM), Raman spectroscopy (RS), and X-ray diffraction (XRD) analysis, which proved the formation of spherical Cu2O nanoparticles (Cu2ONPs; 1500-600 nm) and leaf-like CuO nanostructures (CuONSs; 80-180/400-700 nm, width/length). PyPA isomers were deposited on the surface of NSs, and adsorption was investigated by surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS). The changes of adsorption on the surface of copper oxide NSs caused by the above-mentioned factors were described and the enhancement factor on this substrate was calculated.