The rate of return on education can measure the size of the return on investment in education, which is an important research area related to national development. The purpose of this paper is to analyze and discuss the relationship between education, regional economic development, and related influence variables using a multilayer linear model. CGSS data of 31 provinces and cities in 2021 are chosen as the empirical analysis data, which are divided into east, middle, and west regions according to geographic location, and the differences in industrial development of the three major regions are measured in terms of upgrading of industrial structure, seniorization, rationalization, urbanization, investment in education, and technological development. Create a model to evaluate the impact of industrial structure upgrading on education investment return in each region. Separately, the slope prediction model includes education variables and regional economic development variables to examine the predictive impact of regional economic growth on the return on education investment. The coefficient of the cross-level interaction term between years of education and regional economic development has a value of 0.07829, and it passes the 1% statistical significance test with a significant cross-level interaction effect. It indicates that the higher the degree of regional economic development, the greater the role of educational human capital in promoting residents’ income, i.e., the rise in the degree of regional economic development will significantly increase the return on investment in education.