Regarding the HOR performance, on phosphorene, only the smallest Ptn clusters provide ΔGH* values close to 0. Among the PtGe structures, a high Ge content is required to yield low ΔGH* values. Nevertheless, on most of the 2D surfaces, alloyed clusters exhibit smaller ΔGH* values, indicating higher catalytic activity. This scenario is unexpected because usually doping or alloying Pt with a second element improves sintering or poisoning resistance, but at the expense of the catalytic activity. In this case, equimolar Pt5Ge5 clusters are predicted to be more active for the HOR. Both Ge alloying and support modifications have been proven to be accessible parameters in the design of active sites and reaction pathways.