The hydrogen evolution reaction (HER) is a critical reaction in addressing climate change; however, it requires catalysts to be generated on an industrial scale. Nanomaterials offer several advantages over conventional HER catalysts, including the possibility of atomic precision in tailoring the intrinsic activity. Ligand-protected metal clusters, such as the thiolate-protected MAu24(SR)18 (where M is Au, Cu, Pd), are of particular interest as not only are they electrocatalytically active toward HER, but the charge state and composition can be precisely tuned. Here, we present a comprehensive computational study examining how the charge state and dopants affect the catalytic activity of [MAu24(SCH3)18]q toward the Volmer step of the HER. Assuming an adsorbed hydrogen atom to be the key intermediate, then, according to the Sabatier principle, the H adsorption energy should be nearly thermoneutral for an ideal HER catalyst. Our results show that adsorption energies alone are an insufficient criterion to identify a promising catalytic material; experimentally relevant redox potentials, the corresponding catalyst’s charge states, and the kinetic barriers should also be considered. Notably, this work explains the relative activity of MAu24(SR)18 (M = Au, Cu, Pd) clusters reported by Kumar et al. (Nanoscale 2020, 12, 9969). Our results validate a more thorough computational approach that includes charge and redox potential to understand and screen electrocatalytically active nanoclusters.