This proceedings volume gathers selected, peer-reviewed papers presented at the 2nd International Conference on Mathematics and its Applications in Science and Engineering – ICMASE 2021, which was virtually held on July 1-2, 2021 by the University of Salamanca, Spain. Works included in this book cover applications of mathematics both in engineering research and in real-world problems, touching topics such as difference equations, number theory, optimization, and more. The list of applications includes the modeling of mechanical structures, the shape of machines, and the growth of a population, expanding to fields like information security and cryptography. Advances in teaching and learning mathematics in the context of engineering courses are also covered.