The ten-volume set LNCS 12949 – 12958 constitutes the proceedings of the 21st International Conference on Computational Science and Its Applications, ICCSA 2021, which was held in Cagliari, Italy, during September 13 – 16, 2021. The event was organized in a hybrid mode due to the Covid-19 pandemic.The 466 full and 18 short papers presented in these books were carefully reviewed and selected from 1588 submissions. Part X of the set includes the proceedings of the following workshops: International Workshop on Smart and Sustainable Island Communities (SSIC 2021); International Workshop on Science, Technologies and Policies to Innovate Spatial Planning (STP4P 2021); International Workshop on Sustainable Urban Energy Systems (SUREN-SYS 2021); International Workshop on Ports of the future - smartness and sustainability (SmartPorts 2021); International Workshop on Smart Tourism (SmartTourism 2021); International Workshop on Space Syntax for Cities in Theory and Practice (Syntax_City 2021); International Workshop on Theoretical and Computational Chemistryand its Applications (TCCMA 2021); International Workshop on Urban Form Studies (UForm 2021); International Workshop on Urban Space Accessibility and Safety (USAS2021); International Workshop on Virtual and Augmented Reality and Ap-plcations (VRA 2021); International Workshop on Advanced and Computational Methods for Earth Science applications (WACM4ES 2021).