The commercialization of MXene-based electrodes for sodium ion capture in aqueous solutions is limited by poor stability, which is attributed to edge and surface defects. In this study, 3D Ti3C2Tx MXene hollow microsphere (MHM) is constructed, and a systematic defect passivation and transformation approach is presented to achieve the high stability of MHM when employed as electrode material in capacitive desalination (CDI). Metal atom vanadium (V) and non-metal atoms nitrogen (N) and sulfur (S) are meticulously selected to modulate the defect environment of Ti3C2Tx MXene. The doping mechanism is thoroughly investigated using X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) analysis for the first time: N and S atoms substitute the carbon and replace oxidizable surface groups, V atom bonds with carbon and oxygen and is trapped by Ti vacancy defects. This approach effectively passivates the oxidizable defects and transforms them into new heteroatomic doping defects, leading to the regulation of electronic structure and creation of additional active sites, which enhances stability and sodium capture efficiency for CDI. The optimized N, S, and V co-doped MHM (N, S, V-MHM) electrode shows high electrosorption capacity and rate (141.77 mg g−1 and 2.36 mg g−1 min−1 at 1.2 V) with outstanding cycling stability. In situ EQCM-D measurement underscores the critical role of hydrated sodium ions de/adsorption during charging/discharging processes. This work elucidates a pathway for constructing high-performance and ultra-stable MXene-based electrodes through defect passivation and transformation.