This book constitutes the refereed proceedings of the 22nd Smoky Mountains Computational Sciences and Engineering Conference on Accelerating Science and Engineering Discoveries Through Integrated Research Infrastructure for Experiment, Big Data, Modeling and Simulation, SMC 2022, held virtually, during August 23–25, 2022.The 24 full papers included in this book were carefully reviewed and selected from 74 submissions. They were organized in topical sections as follows: foundational...