Milan has earned a high-profile reputation as a centre of advanced functions, in addition to being an international capital of fashion and design. However, both internal and external challenges are putting strains on Milan’s aspiration to become a southern European and Mediterranean hub.  This review highlights Milan’s potential to capitalise on its advanced services to bolster the regional innovation dynamics and to fuel national growth. It also points out that failure to accelerate the innovation process and to enhance the region’s attractiveness as well as its capacity to implement flagship projects could prove costly. Finally, it calls for rapid metropolitan governance reforms to design and to implement a competitiveness strategy for the entire metropolitan region.