The present book contains the articles published in the Special Issue “Differential Equation Models in Applied Mathematics: Theoretical and Numerical Challenges” of the MDPI journal Mathematics. The Special Issue aimed to highlight old and new challenges in the formulation, solution, understanding, and interpretation of models of differential equations (DEs) in different real world applications. The technical topics covered in the seven articles published in this book include: asymptotic properties of high order nonlinear DEs, analysis of backward bifurcation, and stability analysis of fractional-order differential systems. Models oriented to real applications consider the chemotactic between cell species, the mechanism of on-off intermitte...