Herein, Co₂Mo₃O₈/Nb₂O₅ heterojunctions with rich oxygen vacancies wrapped in cobalt embedded carbon hollow cubic nanoboxes (Co(Mo,Nb)@MCNBs) derived from metal-organic frameworks (MOFs) is synthesized by hydrothermal reaction, bimetallic cation doping, high-temperature carbonization. The synergistic effect and strong electron coupling interaction between Co₂Mo₃O₈/Nb₂O₅ heterojunctions and cobalt embedded carbon hollow cubic nanoboxes result in a more uniform distribution of heterojunctions on the surface of Co@MCNBs, more catalytic active sites are exposed and the catalytic performance is improved. It only requires an overpotential of 284 mV to drive the current density of 10 mA cm⁻² towards oxygen evolution reaction (OER), which is significantly lower than most previously reported catalysts and commercial RuO₂. Furthermore, the Co(Mo,Nb)@MCNBs exhibits exceedingly good long-term stability with the current density retention rate of 98.1% after 43,200 s for OER, which even still outperform the commercial RuO₂ catalyst. More interestingly, the electrolyzer Co(Mo,Nb)@MCNBs(+)||Co@MCNBs(-) demonstrates an excellent cycling stability and outperforms RuO₂(+)||Pt/C(-), suggesting the actual availability of Co(Mo,Nb)@MCNBs in overall water splitting. The synergic effect of heterostructures design of the Co(Mo,Nb)@MCNBs catalyst for overall water splitting will promote the mass production of hydrogen with high-efficiency and low-cost.