This book constitutes the refereed proceedings of the 21st International Symposium on Knowledge and Systems Sciences, KSS 2022, held in Beijing, China, in June 2022.<p>The 14 revised full papers and 3 short paper presented were carefully reviewed and selected from 51 submissions. The papers are organized in topical secions on ​data mining and machine learning; model-based systems engineering; complex systems modeling and knowledge technologies.</p>