Circular Economy (CE) offers insights to sustainable production and consumption by integrating environmental analysis to the socioeconomic system. To promote sustainable development in Guangdong Province, this study integrates System Dynamics (SD) and Material Flow Analysis (MFA) into CE theories to establish a framework to comprehensively evaluate regional economies. Nine development scenarios are further developed to provide strategic recommendations for the development of CE in Guangdong. The results of these scenarios show that the CE of Guangdong is most effective among the nine scenarios when the birth rate is reduced by about 2‰, the growth rates of the primary and secondary industries are reduced by 2%, and the growth rate of the tertiary industry increased by 2%. The biological substance consumption, fossil fuel consumption, building mineral consumption, industrial exhaust emissions and solid waste emissions are 88.39 Mt, 86.63 Mt, 108.16 Mt, 280.90 Mt, and 69.02 Mt respectively. The total material input (TMI) of 10,000 RMB of GDP and the total material output (TMO) of 10,000 RMB of GDP are 49.64 kt/10,000 RMB and 42.70 kt/10,000 RMB in 2022 respectively. Based on the status quo and simulated results, this study acknowledges the importance of population control and highlights the vigorous development of tertiary industry in economic construction. Policy interventions such as building pilot demonstrative smart cities and industrial parks would facilitate long-term sustainability of urban systems.