Metal nanocrystals (NCs) with controlled compositional and distributional structures have gained increasing attention due to their unique properties and broad applications, particularly in fuel cell systems. However, despite the significant importance of composition in metal NCs and their electrocatalytic behavior, comprehensive investigations into the relationship between atomic distribution and electrocatalytic activity remain scarce. In this study, we present the development of four types of nanocubes with similar sizes and controlled compositions (Pd–Pt alloy, Pd@Pt core–shell, Pd, and Pt) to investigate their influence on electrocatalytic performance for methanol oxidation reaction (MOR). The electrocatalytic activity and stability of these nanocubes exhibited variations based on their compositional structures, potentially affecting the interaction between the surface-active sites of the nanocrystals and reactive molecules. As a result, leveraging the synergistic effect of their alloy nanostructure, the Pd–Pt alloy nanocubes exhibited exceptional performance in MOR, surpassing the catalytic activity of other nanocubes, including Pd@Pt core–shell nanocubes, monometallic Pd and Pt nanocubes, as well as commercial Pd/C and Pt/C catalysts.