The significance of Regional Innovation Systems (RIS) as a strategic tool for enhancing a region’s competitiveness has been increasingly recognized. This paper presents a model of RIS that was developed using the system dynamics (SD) methodology. The goal of this model is to amalgamate the systemic approach with computer modeling and simulation disciplines into a comprehensive dynamic framework for analyzing RIS. Within this framework, the paper explores the impact of smart technologies on regional development through the RIS. Specifically, the SD model serves as an ‘experimental tool’ for conducting extensive what-if scenario analyses concerning smart technologies. The efficacy of these technologies is examined in terms of their dynamic influence on regional development, with insights derived from simulation outcomes. Data from two Greek regions provides a strategic analysis over a designated time horizon.