Fermentation has historically played an important role in the production of several commodities such as bread and alcoholic beverages. Today, fermentation is also used to produce specific flavor compounds in multiple industries. Flavor compounds are secondary metabolites produced during fermentation in addition to primary metabolites, such as ethanol. Secondary metabolism is influenced by fermentable carbon, nitrogen makeup, and the fermentation environment. A better understanding of how these variables affect the physiology of yeast strains to produce flavor compounds may improve several industrial commodities. To this end, systems biology represents an attractive strategy for studying the complex dynamics of secondary metabolism. Although applying systems biology methods to winemaking or brewing is not a new concept, directly linking -omics data with the production of flavor compounds represents a novel approach to improving flavor production in fermentation. Thus far, the bulk of the work in which systems biology methods have been applied to fermentation has relied heavily on laboratory strains of Saccharomyces cerevisiae that lack metabolism-relevant genes present in industrial yeast strains. Therefore, investigations of industrial strains with systems biology approaches will provide a deeper understanding of secondary metabolism in industrial settings. Ultimately, integrating multiple -omics approaches will lay the foundation for predictive models of S. cerevisiae fermentation and optimal flavor production.