This study explores the impact of Cu and Ni doping on the structural, wettability, optical, and photocatalytic properties of ZnO thin films. The co-doped thin films, with varying Ni concentrations, were deposited using a spray pyrolysis method onto pre-heated soda lime glass substrates. X-ray diffraction analysis confirmed the hexagonal wurtzite structure with preferred orientation primarily along the (002) plane, while crystallinity decreased with higher Ni concentrations. Scanning electron microscopy reveals a compact, adherent structure in all films, with Ni incorporation altering the surface morphology. Fourier transform infrared spectroscopy identified characteristic absorption bands for metal-oxygen bonds. Optical analysis indicated that all thin films exhibited over 88% average transmittance in the visible region, accompanied by a red shift in the optical bandgap. Photoluminescence spectra exhibited a broad emission band in the visible region, indicating intrinsic and extrinsic defects induced by doping. Co-doping transforms the wettability character of ZnO thin films from hydrophilic to hydrophobic. Finally, the photodegradation efficiency of the thin films against methylene blue under sunlight significantly increases from 72% to 92% with an increase in Ni concentration.