The structural and electronic properties of sphalerite (ZnS) are strongly dependent on the presence of trace metal substituents, which thereby impact the industrial applicability of this important semi-conducting mineral phase. Cadmium (a 4d transition metal) commonly substitutes into the sphalerite mineral structure, yet the geochemical effects of this substitution reaction have not been fully defined. Here we present novel Raman and X-ray Diffraction (XRD) data collected from Cd-bearing synthetic sphalerite samples which explicitly test the influences of Cd substitution on the crystal structure and the surface bonding environment of the ZnS host molecular cluster. The XRD analyses revealed significant shifts in the measured Bragg’s peak positions, which manifest as a linear increase in the calculated unit cell parameter for sphalerite as a function of the local distortions arising from the increasing Cd concentration. These structural and chemical changes are further reflected in the Raman spectra, in which Cd substitution gives rise to a new Raman active mode occurring at 295 cm−1 and which we attribute to Cd-S bond vibrations. The intensity ratio between this Cd-S bond vibrational mode, and the Transverse Optic (TO) mode of the Zn-S bond correlates positively (r2 = 0.9403) with the concentration of Cd substituted into the sphalerite structure. Our work thus highlights the applicability of Raman spectroscopy for identifying the presence and concentration of Cd in sphalerite, and in doing so, fills an existing knowledge gap related to the influence of Cd on the vibrational characteristics of this important semi-conducting mineral phase.