Surface enhanced Raman spectroscopy (SERS) is a reliable, non-destructive, and label-free analytical technique as an alternative to conventional chromatographic, spectroscopic and electroanalytical techniques. In this study, we report a low-cost, rapid, and facile approach for surface-growth of Cu nanostructures (NSs) to serve as a substrate in SERS applications. Our novel approach is based on direct growth of Cu NSs from Au nanoparticles (NPs) that were attached to the substrate through a layer of end-grafted poly(ethylene glycol). The fabricated substrate allowed for determination of trace levels of rhodamine 6G with an analytical enhancement factor of 2.96 x 10 (5) and relative standard deviation of 9.4%. The high-density growth of Cu NSs with close-proximity together with the self-hydrophobicity of the substrate contributed to the SERS activity. Application of the substrate in sensing of drug molecules is demonstrated through tamoxifen, which is widely used for the treatment of cancer. These results show the promise of solid substrates decorated with low cost and abundant Cu NSs for SERS applications.