Since MXenes’ discovery in 2011 (patent priority [1]), they have received tremendous attention in the scientific community [2, 3]. Numerous studies have shown that MXenes hold great potential in various applications, including supercapacitors, lithium-ion batteries, non-lithium-ion batteries, catalysis, photocatalysis, hydrogen production, methane absorption, metal-, ceramic- and polymer-based nanocomposites, field-effect transistors, transparent conductors, biomaterials, active agents for cancer treatment, and many more. In many of these applications, they also outperform other 2D layered materials. However, ongoing research and application of MXenes in different fields bring many challenges, which need to be tackled in the near future. This chapter aims to give an overview of challenges regarding MXenes’ application in various fields and emphasize some potential solution strategies.