¿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 proceedings were carefully reviewed and selected from 1588 submissions. The books cover such topics as multicore architectures, mobile and wireless security, sensor networks, open source software, collaborative and social computing systems and tools, cryptography, human computer interaction, software design engineering, and others. Part III of the set icludes papers on Information Systems and Technologies and the proceeding of the following workshops: International Workshop on Automatic landform classification: spatial methods and applications (ALCSMA 2021), International Workshop on Application of Numerical Analysis to Imaging Science (ANAIS 2021), International Workshop on Advances in information Systems and Technologies for Emergency management, risk assessment and mitigationbased on the Resilience concepts (ASTER 2021), International Workshop on Advances in Web Based Learning (AWBL 2021).