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, blockchain, mobile and wireless security, sensor networks, open source software, collaborative and social computing systems and tools, cryptography, applied mathematics human computer interaction, software design engineering, and others. Part IX of the set includes the proceedings of the following events: 13th International Symposium on Software Engineering Processes and Applications (SEPA 2021); International Workshop on Sustainability Performance Assessment: models, approaches and applications toward interdisciplinary and integrated solutions (SPA 2021).