The construction of binder-free electrodes with well-defined three-dimensional (3D) morphology and optimized electronic structure represents an efficient strategy for the design of high-performance electrocatalysts for the development of efficient green hydrogen technologies. Herein, Ru nanocrystals were modified on 3D interconnected porous FeOOH nanostructures with open network-like frameworks on NiFe foam (Ru/FeOOH@NFF), which were used as an efficient electrocatalyst. In this study, a 3D interconnected porous FeOOH with an open network structure was first electrodeposited on NiFe foam and served as the support for the in-situ modification of Ru nanocrystals. Subsequently, the Ru nanocrystals and abundant oxygen vacancies were simultaneously incorporated into the FeOOH matrix via the adsorption-reduction method, which involved NaBH4 reduction. The Ru/FeOOH@NFF electrocatalyst shows a large specific surface area, abundant oxygen vacancies, and modulated electronic structure, which collectively result in a significant enhancement of catalytic properties with respect to the oxygen evolution reaction (OER) and urea oxidation reaction (UOR). The Ru/FeOOH@NFF catalyst exhibits an outstanding OER performance, requiring a low overpotential (360 mV) at 200 mA cm−2 with a small Tafel slope (58 mV dec-1). Meanwhile, the Ru/FeOOH@NFF catalyst demonstrates more efficient UOR activity for achieving 200 mA cm−2 at a lower overpotential of 272 mV. Furthermore, an overall urea electrolysis cell using the Ru/FeOOH@NFF as the anode and Pt as the cathode (Ru/FeOOH@NFF||Pt) reveals a cell voltage of 1.478 V at 10 mA cm−2 and a prominent durability (120 h at 50 mA cm−2). This work will provide a valuable understanding of the construction of high-performance electrocatalysts with 3D microstructure for promoting urea-assisted water electrolysis.