Mathematical problems in the aerospace industry deeply affect the development of many related fields, such as aerodynamics, astrodynamics, deep space exploration, space environment, manned space flight, space traffic management, etc. As a result, these challenges have together become a hotbed of research and have garnered significant attention in recent years. However, notwithstanding the enormous efforts of mathematicians, natural scientists, and engineers, many major issues remain unresolved. Therefore, there is an urgent need to provide a comprehensive introduction to the major mathematical problems in aerospace in order to help people refer to and conduct further in-depth research. This reprint thus contains a systematic review and several technical studies regarding the latest major mathematical problems in aerospace and their respective applications in different fields. This Special Issue aspires to make a valuable contribution to the knowledge on the mathematical theories, computational methods, and other issues relating to aerospace.