The vigorous development of cross-border RMB business is an important way to promote RMB internationalization and provide a new path for the diversified development of the city clusters in Macao and Zhuhai. Foreign exchange reserves and assets in the form of foreign currency are the main assets of Macao, but in recent years, due to the downturn in tourism, the percentage of cross-border RMB trade settlement in Macao’s current account has been decreasing year by year, and its scale has been shrinking. At the same time, Macao’s imports from Portuguese-speaking countries are on the rise, which is the basis for the development of RMB settlement for Macao’s trade with Portuguese-speaking countries. In the future, when promoting cross-border RMB business, Macao needs to cooperate with Zhuhai to improve RMB financial infrastructure and promote the establishment of an RMB clearing center for Portuguese-speaking countries. For their cooperation, we should view Macao as a window and Hengqin as a strategic extension to promote trade with other countries along the “Belt and Road”, increase mutual investment and labor cooperation, and focus on the development of characteristic tourism.