This paper suggests a tentative conceptual framework to study the internationalization of OECD-based SMEs (Small and Medium-sized Enterprises) attracted by fast growing emerging markets, and the supportive role of global cities as market gate focal points providing a wide range of financial and non-financial services facilitating market entry. The hypothesis is that a number of global cities (about 75 cities are classified and ranked as such worldwide) play an important business intermediation role, including vis-à-vis distant and difficult emerging markets. This article is to bring up first-hand SME empirical research added value to the study of global cities, which has been envisaged so far exclusively in terms of their global growth as contributed by transnational corporations. As a matter of fact, the existing literature reveals that the business intermediation role of global cities has been studied exclusively in terms of services provided to transnational corporations and their affiliates, which tend to concentrate their regional offices and other business coordinating logistics and management in such cities. Such business intermediation role made by global cities for foreign SMEs has not been investigated so far. For instance, the interlink between SMEs and the entrepreneurship eco-system of global cities has been tentatively explored in an empirical contribution by Acs (2008) derived from Global Entrepreneurship Monitor data. The first part of this contribution aims to propose a conceptual framework that combines studies in international business management with a strong focus on SME internationalization on the one hand, together with knowledge from economic geography and urban studies with a focus on global cities on the other hand. In the second part of this paper, an empirical study of Swiss SME internationalization vis-a-vis distant Asian emerging markets and their relative direct and indirect presence in so-called alpha-type global cities provides some first-hand empirical evidence validating the proposed conceptual framework. The findings tend to demonstrate the high importance of global cities for European internationalizing SMEs – as illustrated in the Swiss case - especially but not exclusively vis-a-vis emerging markets.