With the rising tide of globalization, urban branding campaigns have become the focal points of decision makers and planners aiming to establish city reputations and to achieve long-term urban prosperity. This paper, therefore, aims to develop a sustainability-oriented city branding framework that incorporates (1) comprehensive perceptions from various stakeholders through questionnaires and (2) empirical applications that evaluate the city-level potentials for a global mega-region in support of its sustainable growth. Seven major aspects, i.e., economic development, environment, potential, pulse, people, infrastructure, and governance, have been identified and assessed in the context of 26 prefecture cities in the Yangtze River Delta region. Moreover, a cluster analysis differentiated these cities into four groups with distinct characteristics and development paths. Through the framework and evaluation outputs, local planners, researchers, and decision-makers would be better placed to design and implement sustainable policy packages and incentives, with a quantitative insight into current strengths and weaknesses.