The assessment of regional economic security (RES) is mainly based on the theoretical ideas of political economy and marginalism, and the research areas are mainly concentrated in European and American countries/regions, especially Eastern Europe. Taking the Qinghai–Tibet Plateau in China as an example, this paper constructs a triple-dimensional analytical framework, resources, and environmental–economic foundation-driving forces, based on the institutional approach of economic geography, with the purpose of making up for the deficiency of the extant literature, which pays little attention to regional characteristics and the dynamic mechanism concerning RES, and to provide a tool to identify key factors affecting RES. This paper obtained the main conclusions as follows. (1) The index of the economic security in the Qinghai–Tibet Plateau is on the rise, and the difference at the level of RES among cities is significant but tends to decrease. (2) There is a significant spatial autocorrelation among cities in the Qinghai–Tibet Plateau in terms of RES. The high-value areas are concentrated along the southeast edge, and the low-value areas are concentrated in the central areas of the west. (3) Despite lower weight values, the weakness of the economic foundation and the fragility of the ecological environment has increasingly hampered the improvement of the economic security in the Qinghai–Tibet Plateau. In terms of driving forces, it is the support of the central government and aid programs of other provinces that contributes to its economic development.