Most host organisms undergo metabolic changes in response to pathogens, environmental cues or simply to boost their immunity. Metabolic modulation has therefore been exploited by both host and pathogens to outwit the other during host–pathogen interactions. Recent studies have revealed that a growing number of metabolites and metabolic processes in crustaceans are crucial in host–pathogen interactions. Here, we reviewed recent work on metabolic changes during immune response of crustaceans and the metabolic reprogramming that takes place in the host induced by pathogens, environmental cues or as a host strategy to withstand these changes or clear the pathogen. In aquaculture crustaceans, limited studies exist on this subject; hence, we will also highlight themes for possible future research on metabolite reprogramming and how this strategy can be leveraged to improve sustainable aquaculture and enhance crustaceans’ response to pathogens and environmental changes.