Rational design of highly stable and active metal catalysts requires a deep understanding of metal-support interactions at the atomic scale. Here, ultrathin films of FeO and FeO 2- x grown on Pt(111) are used as templates for the construction of well-defined metal nanoclusters. Periodic arrays of Cu clusters in the form of monomers and trimers are preferentially located at FCC domains of FeO/Pt(111) surface, while the selective location of Cu clusters at FeO 2 domains is observed on FeO 2- x /Pt(111) surface. The preferential nucleation and formation of well-ordered Cu clusters are driven by different interactions of Cu with the Fe oxide domains in the sequence of FeO 2 -FCC > FeO-FCC > FeO-HCP > FeO-TOP, which is further validated by density functional theory calculations. It has been revealed that the p -band center as a reactivity descriptor of surface O atoms determines the interaction between metal adatoms and Fe oxides. The modulated metal-oxide interaction provides guidance for the rational design of supported single-atom and nanocluster catalysts.