ZnS has great potentials as an anode for lithium storage because of its high theoretical capacity and resource abundance; however, the large volume expansion accompanied with structural collapse and low conductivity of ZnS cause severe capacity fading and inferior rate capability during lithium storage. Herein, 0D-2D ZnS nanodots/Ti3C2Tx MXene hybrids are prepared by anchoring ZnS nanodots on Ti3C2Tx MXene nanosheets through coordination modulation between MXene and MOF precursor (ZIF-8) followed with sulfidation. The MXene substrate coupled with the ZnS nanodots can synergistically accommodate volume variation of ZnS over charge–discharge to realize stable cyclability. As revealed by XPS characterizations and DFT calculations, the strong interfacial interaction between ZnS nanodots and MXene nanosheets can boost fast electron/lithium-ion transfer to achieve excellent electrochemical activity and kinetics for lithium storage. Thereby, the as-prepared ZnS nanodots/MXene hybrid exhibits a high capacity of 726.8 mAh g−1 at 30 mA g−1, superior cyclic stability (462.8 mAh g−1 after 1000 cycles at 0.5 A g−1), and excellent rate performance. The present results provide new insights into the understanding of the lithium storage mechanism of ZnS and the revealing of the effects of interfacial interaction on lithium storage performance enhancement.