Highly roughened Au-decorated 3D ZnO nanostructures were prepared using a combination of prism holographic lithography and atomic layer deposition techniques. The optimized SERS intensity from the prepared Au-coated 3D ZnO inverse structures was twenty times the intensity obtained from an Au-coated flat glass control substrate. The surfaces could be reused after the photocatalytic degradation and removal of adsorbates in the presence of ZnO. The Au-coated 3D ZnO structures described here offer an alternative to traditional single-use SERS substrates.