Streptococcus suis, both a common colonizer of the porcine upper respiratory tract and an invasive pig pathogen, successfully adapts to different host environments encountered during infection. Whereas the initial infection mainly occurs via the respiratory tract, in a second step, the pathogen can breach the epithelial barrier and disseminate within the whole body. Thereby, the pathogen reaches other organs such as the heart, the joints, or the brain. In this review, we focus on the role of S. suis metabolism for adaptation to these different in vivo host niches to encounter changes in nutrient availability, host defense mechanisms and competing microbiota. Furthermore, we highlight the close link between S. suis metabolism and virulence. Mutants deficient in metabolic regulators often show an attenuation in infection experiments possibly due to downregulation of virulence factors, reduced resistance to nutritive or oxidative stress and to phagocytic activity. Finally, metabolic pathways as potential targets for new therapeutic strategies are discussed. As antimicrobial resistance in S. suis isolates has increased over the last years, the development of new antibiotics is of utmost importance to successfully fight infections in the future.