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. Part VI of the set includes the proceedings of the following workshops: International Workshop on Digital Transformation and Smart City (DIGISMART 2021); International Workshop on Econometrics and Multidimensional Evaluation in Urban Environment (EMEUE 2021); International Workshop on Transformational Urban Mobility: Challenges and Opportunities During and Post COVID Era (FURTHER2021); International Workshop on Geodesign in Decision Making: meta planning and collaborative design for sustainable and inclusive development (GDM 2021);11th International Workshop on Future Computing System Technologies and Applications (FiSTA 2021); International Workshop on Geographical Analysis, Urban Modeling, Spatial Statistics (GEOG-AND-MOD 2021).