The electro-oxidation of urea (EOU) is a remarkable but challenging sustainable technology, which largely needs a reduced electro-chemical potential, that demonstrates the ability to remove a notable harmful material from wastewater and/or transform the excretory product of humans into treasure. In this work, an Ni2P-nanoparticle-integrated porous nickel oxide (NiO) hetero-structured nanosheet (Ni2P@NiO/NiF) catalyst was synthesized through in situ acid etching and a gas-phase phosphating process. The as-synthesized Ni2P@NiO/NiF catalyst sample was then used to enhance the electro-oxidation reaction of urea with a higher urea oxidation response (50 mA cm−2 at 1.31 V vs. RHE) and low onset oxidation potential (1.31 V). The enhanced activity of the Ni2P@NiO/NiF catalyst was mainly attributed to effective electron transport after Ni2P nanoparticle insertion through a substantial improvement in active sites due to a larger electrochemical surface area, and a faster diffusion of ions occurred via the interactive sites at the interface of Ni2P and NiO; thus, the structural reliability was retained, which was further evidenced by the low charge transfer resistance. Further, the Ni2P nanoparticle insertion process into the NiO hetero-structured nanosheets effectively enabled a synergetic effect when compared to the counter of the Ni2P/NiF and NiO/NiF catalysts. Finally, we demonstrate that the as-synthesized Ni2P@NiO/NiF catalyst could be a promising electrode for the EOU in urea-rich wastewater and human urine samples for environmental safety management. Overall, the Ni2P@NiO/NiF catalyst electrode combines the advantages of the Ni2P catalyst, NiO nanosheet network, and NiF current collector for enhanced EOU performance, which is highly valuable in catalyst development for environmental safety applications.