Foreign direct investment (FDI) is increasingly global and knowledge-intensive, yet research often centres on advanced economies and large multinational enterprises (MNEs). This oversight neglects the diverse economies of the Global South and limits understanding of how smaller MNEs and less technologically advanced cities participate in global FDI flows and technological advancement. This article addresses these gaps by examining how less resource-rich cities of emerging economies transform into investment hubs. It investigates the drivers of FDI from countries at various stages of development into emerging economies, with a particular focus on Medellín’s evolution into an information and communication technologies (ICT) investment hub. The study employs mixed methods to integrate insights from macro-level country attractiveness with local impacts of MNE activities and global policy and planning trends. It provides a multiple-perspective analysis of how cities in emerging economies attract knowledge-intensive MNEs and, drawing on Medellín’s experience, proposes a conceptual model that identifies key strategic activities for the emergence of investment hubs. This model provides a framework for exploring city-specific strategies fostering similar transformations in other emerging economies.