Resource-based regions support national economic development and are essential sources of basic energy and raw materials. In the post-pandemic era, however, there are practical situations to deal with, such as a fractured industrial chain, a weaker industrial structure, and a sharp reduction in economic benefits. Based on data collected from 68 cities in China, from 2010 to 2021, with 816 observations, this paper explores the industrial development process of resource-based regions in China and the change in the toughness of the industrial structure under the impact of COVID-19. The paper studies and analyzes industrial development trends, industrial structure toughness, and spatial spillover effects. The methods used are the Markov chain model and the Industrial Structure Advancement Index. By building the spatial Dubin model, the paper analyzes the spatial spillover effect of regional industrial development. It decomposes the spillover effect using the partial differential model based on regression. The results show that, during the study period, the comprehensive development level of industries in resource-based regions in China was slowly improving and tended to stabilize after entering the post-pandemic era. The evolution of an advanced industrial structure is significantly heterogeneous among regions, and each region has different toughness. The impact of COVID-19 has reduced the toughness of China’s resource-based regions’ industrial structure. The spatial spillover effect of regional industrial development is significant. Labor force, technology input, and industrial-structure optimization have different impacts on the industrial development of neighboring regions. In the post-pandemic era, China has used new management methods for more innovation. In order to achieve low-carbon, environmental protection, and sustainable development of resources, realize the rapid recovery of the toughness of industrial structure in China’s resource-based cities, and reduce the impact of the COVID-19 pandemic, China proposes to expand the supply of resources, improve the allocation of resources, optimize the direction, promote the rational flow and efficient aggregation of various factors, and enhance the impetus for innovation and development.</div