As an emerging star of 2D nanomaterials, 2D transition metal carbides and nitrides, named MXenes, present a large potential in various research areas owing to their intrinsic multilayer structure and intriguing physico‐chemical properties. However, the fabrication and application of functional MXene‐based devices still remain challenging as they are prone to oxidative degradation under ambient environment. Within this review, the preparation methods of MXenes focusing on the recent investigations on their thermal structure–stability relationships in inert, oxidizing, and aqueous environments are systematically introduced. Moreover, the key factors that affect the oxidation of MXenes, such as, atmosphere, temperature, composition, microstructure, and aqueous environment, are reviewed. Based on different scenarios, strategies for avoiding or delaying the oxidation of MXenes are proposed to encourage the utilization of MXenes in complicated environments, especially at high temperature. Furthermore, the chemistry of MXene‐derived oxides is analyzed, which can offer perspectives on the further design and fabrication of novel 2D composites with the unique structures of MXenes being preserved.