This book constitutes the revised selected papers of the 21st European Workshop on Computer Performance Engineering, EPEW 2025, held in Catania, Italy, on June 26, 2025. The 11 papers presented in this volume were carefully reviewed and selected from 15 submissions. These papers present performance evaluation of systems from a theoretical and practical viewpoint. Application of performance evaluation techniques to emerging technologies, like cyber-physical systems ranging from mobile devices and Internet-of-Things (IoT), fog and edge computing, applications to large-scale cloud computing systems, smart grids, security infrastructures, are among the topics of interest to EPEW 2025.