Molecular resonance can be strengthened by charge transfer, profiting chemical mechanism (CM)-related surface-enhanced Raman scattering (SERS). Herein a supramolecular assembly enabled SERS system is established by functionalizing para-sulfonatocalix[4]arene (pSC4) onto Au3Cu nanocrystals (NCs). Due to the cooperation of Au and Cu, pSC4 is directionally assembled on the surface of Au3Cu NCs via van der Waals force, enabling photoinduced and hydrogen bond-induced charge transfer, which remarkably enhances the Raman scattering of methylene blue (MB) captured by pSC4. In particular, for the C-N and C-C stretching of MB, the contributions of resonance Raman scattering increase up to 80%. In addition, the SERS system is able to display affinities of different host-guest interactions, and further employed to evaluate effects of drugs for Alzheimer's disease. In this work, charge transfer is realized by performing supramolecular assembly on the surface of plasmonic nanomaterials, providing an avenue to design CM-related and reporter-tunable SERS systems.