The systemic approach has long since been used for modelling the dynamics of systems of cities. Self-organization principles and differential equations have been broadly applied in the 1980’s. Agent-based models open new ways for simulating cities’ evolution. This paper discusses different registers and levels of explanation when it comes to cities’ growth rates differences. It also shows the interest of the agent approach for formalizing hypotheses at the meso-geographical level of cities. A short state of the art on the concept of system of cities and on the associated spatio-temporal models is given. The EuroSim model, developed with a multi-agent system, is presented. The evolution of European cities is simulated between 1950 and 2050 giving different scenarios on the opening of European borders to outside immigration and on the existence of internal economical barriers.