Designing cost-effective and high-active urea oxidation reaction (UOR) catalysts through interface engineering is highly imperative for the hydrogen economy. Unfortunately, the majority of reported studies focus on empirical exploration and seldom elucidate the modulation principle of interface engineering on the electronic structure for optimizing the catalytic UOR activity, hindering the rational construction of high-performance catalysts. In response, the Ni5P4/NiSe nanoplates with abundant interfaces are experimentally fabricated on the macroporous Ni foam substrate. The density functional theory (DFT) predictions decipher accelerated charge transmission at the Ni5P4/NiSe interfacial area, accompanied by the formation of a moderate d-band center. Subsequently, the dehydrogenation dynamics of the Ni5P4/NiSe heterojunction is effectively improved during the stepwise UOR process. As expected, the elaborate Ni5P4/NiSe exhibits outstanding UOR activity under tough environments (6.0 M KOH with urine or 0.5 M urea), further corroborating its prospects as excellent UOR catalysts for industrial applications.