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This study constructed a multidimensional indicator system to evaluate spatio-temporal heterogeneity of China’s import and export trade of 31 provinces from 2000 to 2022. This study describes the distribution of China’s import and export trade by using location Gini coefficient and exploratory spatial analysis. Additionally, Multiple linear regression was used to ascertain the extent of contribution by various factors on the spatio-temporal heterogeneity of import and export trade. The simulation results show that inter-provincial import and export trade displayed distinct spatio-temporal differentiation characteristics with a prominent east-to-west disparity from 2000 to 2022. The trade links between various regions of the country have gradually strengthened, with a corresponding high correlation to the level of economic development. GDP, financial expenditure, freight transportation volume, technology market turnover, foreign investment, and disposable income of all residents, significantly influence the per capita export and import volume. In general, it is suggested that China and developing countries should take effective measures to promote balanced trade development, strengthen regional cooperation and coordination, and promote green trade and sustainable development.