A simple one-pot approach for the synthesis of gold-loaded copper oxide (Au-CuOx) nanoplates was employed to develop a sensitive electrochemical surface enhanced Raman scattering (EC-SERS) substrate for the detection of anti-cancer drug hydroxycarbamide (HC). HC has been used for decades as a therapeutic agent against sickle cell anaemia and various cancers. The Au-CuOx substrate was characterized using various spectroscopic and imaging techniques, including XRD, XPS, FTIR, TEM and SEM. The electrochemical impact on the SERS-based sensing capability was investigated by immobilizing the bimetallic material on a conductive glass support acting as a working electrode. First-principle calculations were carried out to predict the electrostatic properties, electron transfer contribution and adsorption energetics of HC molecules on the nanostructured surface. Spectroscopic and theoretical investigations suggested that Au-loaded copper oxide exhibits inherent surface plasmon resonance (SPR) properties that can be notably enhanced by incorporating the electrochemical factor. Several prominent Raman peaks associated with HC and ascribed by the NCN bending, CN stretching, NO stretching, CO stretching, and NH2 wagging vibrational modes showed substantial enhancements upon the electrochemically induced interaction between the SERS substrate and the drug molecules. A limit of detection of one-tenth of nanomolar concentration could be achieved under optimum conditions. The presented methodology could be potential in the context of biomedical laboratories for the sake of quick and reliable assessment.