Sustainability is one of the most debated topics of the 21st century, especially regarding innovation. This study analyzes the role of policy-makers in two innovation ecosystems to study how they address sustainability objectives at regional levels. We conduct a comparative case study analysis on two innovative regions, Stockholm (Sweden) and Hovedstaden (Denmark), where sustainability goals are a priority in both countries’ policy strategies. The main results suggest that while the Stockholm region prioritizes the increase of competitiveness and attractiveness level of the region, Hovedstaden focuses mainly on SMEs’ growth and innovation output at the organizational level.