Abstract: Global City-Regions are an important phenomenon of economic geography of the world in the 21st century, and have become the powerful engine of regional economic development in the world. The Yangtze River Delta region as a Global City-region, the paper focuses on the second-tier cities in the periphery of Shanghai, and proposes the concept features of the second-tier city. It thinks that Suzhou, Hangzhou, Nanjing, Wuxi, Ningbo, can be defined as the second-tier cities in the Yangtze River Delta region. Reference development experience of domestic and international typical cities, it analyzes the industrial functions of these second-tier cities and points out that relatively developed manufacturing and service industries is its important characteristics in the Yangtze River Delta region. In Hangzhou, for example, based on the strategic objectives of internationalization, it explore the development path of its manufacturing and service industries, and then put forward the strategic initiative for industrial restructuring and urban functions upgrades.