Recent studies show that some oxide films can remain permeable to reactants, improving activity without significantly obstructing active sites. Yet, their typically amorphous structures and poorly defined metal–oxide interfaces hinder molecular-level understanding. To address this, we employed density functional theory (DFT) calculations combined with advanced structure-searching algorithms to explore well-defined oxide films on single-crystal metal surfaces. High-throughput simulations revealed that specific transition metal oxyhydroxides such as ZnOxHy, MoOxHy, IrOxHy, and WOxHy preferentially decorate either low or high coordinated metal sites. We further demonstrate that the adsorption energies of key intermediates (H, CO, NO, OH) can be effectively tuned through site-selective oxide decoration. These changes arise from both direct chemical interactions with the oxide and electronic modulation of the underlying metal surface. Remarkably, we also observe a switch in the preferred adsorption site for certain intermediate/oxide combinations. Overall, these insights highlight a promising path for designing next-generation catalysts through precise control of metal/oxide interfaces and adsorption site engineering.