The contents of this editorial is proposed in three parts devoted to the modeling and simulation of mutating virus pandemics in a globally connected world. The presentation is as follows: first, a general framework is presented according to the idea that mathematical models should go beyond deterministic population dynamics by considering the multiscale, heterogeneous features of the complex system under consideration; second, the contents of the papers in this issue are presented; finally, there is a critical analysis looking ahead to research perspectives.