Brevibacillus thermoruber 423 is a thermophilic bacterium capable of producing high levels of exopolysaccharide (EPS) that has broad applications in nutrition, feed, cosmetics, pharmaceutical, and chemical industries, not to mention in health and bionanotechnology sectors. EPS is a natural, nontoxic, and biodegradable polymer of sugar residues and plays pivotal roles in cell-to-cell interactions, adhesion, biofilm formation, and protection of cell against environmental extremes. This bacterium is a thermophilic EPS producer while exceeding other thermophilic producers by virtue of high level of polymer synthesis. Recently, B. thermoruber 423 was noted for relevance to multiple industry sectors because of its capacity to use xylose, and produce EPS, isoprenoids, ethanol/butanol, lipases, proteases, cellulase, and glucoamylase enzymes as well as its resistance to arsenic. A key step in understanding EPS production with a systems-based approach is the knowledge of microbial genome sequence. To speed biotechnology and industrial applications, this study reports on a genome-scale metabolic model (GSMM) of B. thermoruber 423, constructed using the recently available high-quality genome sequence that we have subsequently validated using physiological data on batch growth and EPS production on seven different carbon sources. The model developed contains 1454 reactions (of which 1127 are assigned an enzyme commission number) and 1410 metabolites from 925 genes. This GSMM offers the promise to enable and accelerate further systems biology and industrial scale studies, not to mention the ability to calculate metabolic flux distribution in large networks and multiomic data integration.