The three-volume sets constitute the refereed proceedings of the 15th International Conference on Knowledge Science, Engineering and Management, KSEM 2022, held in Singapore, during August 6-8, 2022.  The 169 full papers presented in these proceedings were carefully reviewed and selected from 498 submissions. The papers are organized in the following topical sections: Volume I: Knowledge Science with Learning and AI (KSLA) Volume II:  Knowledge Engineering Research and Applications (KERA) Volume III:  Knowledge Management with Optimization and Security (KMOS)