Commercially available fully spectroscopic pixelated cadmium telluride (CdTe) detector systems have been adopted lately for benchtop x-ray fluorescence (XRF) imaging/computed tomography (XFCT) of objects containing metal nanoprobes such as gold nanoparticles (GNPs). To date, however, some important characteristics of such detector systems under typical operating conditions of benchtop XRF/XFCT imaging systems are not well known. One important but poorly studied characteristic is the effect of detector bias-voltage on photon counting efficiency, energy resolution, and the resulting material detection limit. In this work, therefore, we investigated these characteristics for a commercial pixelated detector system adopting a 1-mm-thick CdTe sensor (0.25-mm pixel-pitch), known as HEXITEC, incorporated into an experimental benchtop cone-beam XFCT system with parallel-hole detector collimation. The detector system, operated at different bias-voltages, was used to acquire the gold XRF/Compton spectra from 1.0 wt% GNP-loaded phantom irradiated with 125 kVp x-rays filtered by 1.8-mm Tin. At each bias-voltage, the gold XRF signal, and the full-width-at-half-maximum at gold Kα 2 XRF peak (∼67 keV) provided photon counting efficiency and energy resolution, respectively. Under the current experimental conditions, the detector photon counting efficiency and energy resolution improved with increasing bias-voltage by ∼41 and ∼29% at −300V; ∼54 and ∼35% at −500V, respectively, when compared to those at −100V. Consequently, the GNP detection limit improved by ∼26% at −300V and ∼30% at −500V. Furthermore, the homogeneity of per-pixel energy resolution within the collimated detector area improved by ∼34% at −300V and ∼54% at −500V. These results suggested the gradual improvements in the detector performance with increasing bias-voltage up to −500V. However, at and beyond −550V, there were no discernible improvements in photon counting efficiency and energy resolution. Thus, the bias-voltage range of −500 to −550V was found optimal under the current experimental conditions that are considered typical of benchtop XRF/XFCT imaging tasks.