The study of extracellular metabolites has been prevalent in scientific literature. However, global exometabolite profiling was only realized with recent advances allowing for improved chromatographic separation and detection of hundreds to thousands of compounds by the mid-2000s. The first work to demonstrate the biological relevance of comparative profiling of exometabolite pools was not until 2003, when the term "metabolite footprinting" was coined by Jess Allen and coworkers. This work attracted a great deal of interest in the community, particularly for characterization of microbial metabolism.  The idea of the "exometabolome" encompassing the components of the exometabolite pool was not introduced until 2005.
Recent advances in mass spectrometry imaging have allowed for spatial localization of released metabolites. As the field of microbiology becomes increasingly more centered on microbial community structure, exometabolomics has provided for rapid understanding of metabolic interactions between two or more species.  Recently, exometabolomics has been used to design co-culture systems.  Because the analysis of extracellular metabolites allows for the predictions and determinations of metabolite exchange, exometabolomics analyses can be used for understanding community ecological networks.