This chapter explores new advances and possible added value to the geo-economic study of global cities from an international business and corporate management perspective. First, this chapter reviews existing literature and knowledge, which reveals that the economic intermediation role of global cities has been mainly studied in terms of localization of transnational corporations (TNCs) and their affiliates and the density of global city service-providers. Global cities present a high concentration of TNC regional/international headquarters and related in-house and outsource logistics. This is counterintuitive knowledge as most predictions anticipated that post-Cold War globalization and the rise of ICT communications would lead to the declining role of global cities as major operational hubs for TNCs. The opposite has happened and global cities have further expanded, even dramatically for some among the 80 global cities ranked as such as of today. Secondly, this chapter explores whether and how far global cities should be also envisaged conceptually and empirically as regional/international hubs for other types of business operators in addition to TNCs. It shows that global cities also provide a wide range of gateway and supportive services enabling the internationalization of smaller firms and transnational SMEs to different regions of the world. However, most of them do not necessarily localize directly and physically in global cities – what is a major difference compared to the presence modes of TNC operations.