This book constitutes the thoroughly refereed post-conference proceedings of the 4th International Conference on High Performance Computing in Science and Engineering, HPCSE 2019, held in Karolinka, Czech Republic, in May 2019. The 9 papers presented in this volume were carefully reviewed and selected from 13 submissions. The conference provides an international forum for exchanging ideas among researchers involved in scientific and parallel computing, including theory and applications, as well as applied and computational mathematics. The focus of HPCSE 2019 was on models, algorithms, and software tools that facilitate efficient and convenient utilization of modern parallel and distributed computing architectures, as well as on large-scale applications.