This book constitutes the proceedings of the 22st International Conference on Embedded Computer Systems: Architectures, Modeling, and Simulation, SAMOS 2021, which took place in July 2022 in Samos, Greece. The 21 full papers presented in this volume were carefully reviewed and selected from 44 submissions. The papers are organized in topics as follows: High level synthesis; memory systems; processor architecture; embedded software systems and beyond; deep learning optimization; extra-functional property estimation; innovative architectures and tools for security; european research projects on digital systems, services, and platforms.