2D MXenes are highly attractive for fabricating high-precision gas sensors operated at room temperature (RT) due to their high surface-to-volume ratio. However, the limited selectivity and low sensitivity are still long-standing challenges for their further applications. Herein, the self-assembly of 0D–2D heterostructure for highly sensitive NO2 detection was achieved by integrating ZnO nanoparticles on Ti3C2Tx MXene-derived TiO2 nanosheets (designated as ZnO@M−TiO2). ZnO nanoparticles can not only act as spacers to prevent the restacking of M−TiO2 nanosheets and ensure effective transfer for gas molecules, but also enhance the sensitivity of the sensor the through trapping effect on electrons. Meanwhile, M−TiO2 nanosheets facilitate gas diffusion for rapid sensor response. Benefiting from the synergistic effect of individual components, the ZnO@M−TiO2 0D–2D heterostructure-based sensors revealed remarkable sensitivity and excellent selectivity to low concentration NO2 at RT. This work may facilitate the sensing application of MXene derivative and provide a new avenue for the development of high-performance gas sensors in safety assurance and environmental monitoring.