This proceedings constitutes the refereed post-conference proceedings of the 13th International Conference on Simulation Tools and Techniques, SIMUTools 2021, held in November 2021. Due to COVID-19 pandemic the conference was held virtually.The 63 revised full papers were carefully selected from 143 submissions. The papers focus on new results in the field of system modeling and simulation, software simulation, communication networks’ modeling and analysis, AI system simulation and performance analysis, big data simulation analysis, addressing current and future trends in simulation techniques. They are grouped in thematic aspects on wireless communication, big data, modeling and simulation, deep learning, network simulation and life and medical sciences.