We report the stepwise in-situ manipulation of a nickel cubane nanocluster capped with a specially designed multidentate ligand [Ni^II₄(HL)₃(CH₃O)(CH₃OH)₃](CH₃COO) (Ni4, H₃L = (E)-3-((2-hydroxy-3-methoxybenzylidene)amino)propane-1,2-diol) to firstly [Ni^II₄(HL)₃(CH₃O)(CH₃OH)₂(H₂O)](CH₃COO) (Ni4-1min) and finally to [Ni^II₄(HL)₃ (CH₃O)(H₂O)₃](CH₃COO) (Ni4-20h) during the urea electrolysis. A combination of mass spectrometry, single crystallography and Pair Distribution Function were employed to analyze the structural correlations of this catalyst in crystal/solution/gas phases for confirming the dynamic ligand replacement while preserving the cubic Ni4 core during catalysis. The key feature of their structures is that: i) three ligands wrap the Ni4O4 cubane center on one side forming the rounded outside of a calix; ii) the opposite flat side containing labile methanol as the active site. This structure facilitates the binding of the substrate to the active central nickel atoms during catalysis. Furthermore, due to the different modes of packing, the structure of Ni4-20h sustains 2D net of open space while the structures of Ni4 and Ni4-1min have only closed void inaccessible to solvent molecules or ions. Interestingly, the overpotential initially decreased (up to 45 minutes) until it is stabilized. The result showed a low potential of 1.32 V (UOR) at 10 mA cm^–2 as reflected in the Gibbs free energy decrease of ~0.4 eV from Ni4 to Ni4-20h. This work demonstrates a convincing approach for elucidating the exact nature of the active clusters in electrocatalytic process, and confirms that in-situ modification of electrode materials might alter the direct electronic interaction between substrate and active sites in improving the catalytic performance.