Atomic‐level manipulation of catalysts is important for both fundamental studies and practical applications. Here, the central metal atom in an atomically precise Ag25 nanocluster (NC) is replaced with a single Pd, Pt, and Au atom, respectively, and employed as a model system to study the structure–property–activity relationship at the atomic level. While the geometric structures are well‐preserved after doping, the electronic structures of Ag25 NCs are significantly altered. The combination of Ag25 and TiO2 enhances the charge separation at the interface, exhibiting a 10 times higher hydrogen production rate in photocatalytic hydrogen evolution reaction compared to bare TiO2. Further results show that heteroatoms doping has a negative impact on performance, particularly in the cases of Pd and Au doping. Ultraviolet photoelectron spectroscopy measurements and density functional theory calculations suggest that the lower activities are due to an energy mismatch between the levels of doped NCs and TiO2. These findings not only reveal the impact of heteroatoms doping on the electronic properties and photocatalytic activities of NCs, but can also guide the design of heterometallic NCs for photocatalytic applications
