Inter-city competition has intensified and entrepreneurial regimes have become more popular for urban governance in the age of globalization. It is generally assumed that cities are in competition resulting in a zero-sum game. With a few exceptions, inter-city competition is considered a negative phenomenon, which can affect both cities and their wider regions negatively. But there is inadequate explanation for the emergence of such keen competition or solutions to such a situation. Indeed, cities often have close demographic, social and economic relations. They may also cooperate to enhance the competitive advantage of both cities. Currently there is no integrated study on inter-city competition and cooperation within a region. Furthermore, previous studies on inter-city competition and cooperation have focused on the initiatives led by city governments, whilst ignoring social relations and market-based economic relations. This chapter provides a holistic perspective in the examination of inter-city competition and cooperation that accounts for inter-city social, economic and governmental relations. The relations between Hong Kong and Shenzhen provide a good case for detailed study of inter-city competition and cooperation under regionalization and globalization. The chapter attempts to address a number of questions relating to inter-city competition and cooperation by differentiating inter-city relations at the macro level and firm level and separating the roles of firms and the city governments. This is achieved by reviewing the development of Hong Kong and Shenzhen and developing a conceptual framework to analyse the inter-city relationships. From this analysis implications for policy and future development are produced.