The perfect combination of information and convenient transportation reveals an essential feature of the e-commerce operation modes, that is the combination of virtual and reality. Based on this situation, the paper synthetically uses the research methods of mechanism analysis, BP neural network and spatial panel econometric to explore the effect on regional innovation performance and spatial spillover under e-commerce operation modes. The empirical results indicate that positive spatial autocorrelation was significantly and strengthened in regional innovation of high-tech industry. Second, both informational and convenient transportation showed an exponent function relationship with regional innovation. And the perfect combination of information and convenient transportation improved spatial spillover effect on regional innovation significantly. Third, the higher informational development level improved regional innovation development more significantly and strengthened, the effect is steady and increasing the spatial spillover on regional innovation greatly. Fourth, convenient transportation degree improved regional innovation development significantly and decreased, the effect is unstable and can’t improve the spatial spillover significantly. At the end, some suggestions were given to improve regional innovation development level from the angle of conceptual design, such as strengthen the intensity of supervision and construction in the regional integration process, emphasize the training and using of talents like technology broker and expert in database.