The COVID-19 pandemic has caused effects in many sectors, including in businesses and enterprises. The most vulnerable businesses to COVID-19 are micro, small, and medium enterprises (MSMEs). Therefore, this paper aims to analyze the business vulnerability of MSMEs in Indonesia using the fuzzy spatial clustering approach. The fuzzy spatial clustering approach had been implemented to analyze the social vulnerability to natural hazards in Indonesia. Moreover, this study proposes the Flower Pollination Algorithm (FPA) to optimize the Fuzzy Geographically Weighted Clustering (FGWC) in order to cluster the business vulnerability in Indonesia. We performed the data analysis with the dataset from Indonesia’s national socioeconomic and labor force survey (SUSENAS and SAKERNAS). We first compared the performance of FPA with traditional FGWC, as well as several known optimization algorithms in FGWC such as Artificial Bee Colony, Intelligent Firefly Algorithm, Particle Swarm Optimization, and Gravitational Search Algorithm. Our results showed that FPAFGWC has the best performance in optimizing the FGWC clustering result in the business vulnerability context. We found that almost all of the regions in Indonesia outside Java Island have vulnerable businesses. Meanwhile, in most of Java Island, particularly the JABODETABEK area that is the national economic backbone, businesses are not vulnerable. Based on the results of the study, we provide the recommendation to handle the gap between the number of micro and small enterprises (MSMEs) in Indonesia.