In the past few decades, despite all the significant achievements in industrial microbial improvement, the approaches of traditional random mutation and selection as well as the rational metabolic engineering based on the local knowledge cannot meet today's needs. With rapid reconstructions and accurate in silico simulations, genome-scale metabolic model (GSMM) has become an indispensable tool to study the microbial metabolism and design strain improvements. In this review, we highlight the application of GSMM in guiding microbial improvements focusing on a systematic strategy and its achievements in different industrial fields. This strategy includes a repetitive process with four steps: essential data acquisition, GSMM reconstruction, constraints-based optimizing simulation, and experimental validation, in which the second and third steps are the centerpiece. The achievements presented here belong to different industrial application fields, including food and nutrients, biopharmaceuticals, biopolymers, microbial biofuel, and bioremediation. This strategy and its achievements demonstrate a momentous guidance of GSMM for metabolic engineering breeding of industrial microbes. More efforts are required to extend this kind of study in the meantime.