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)