With a frequent occurrence of approximately 10.6% in adult populations, anxiety disorders are among the most common mental health problems worldwide. Although anxiety disorders are rather prevalent, their underlying biochemical mechanisms remain unclear. As a functional endpoint of all biological events, the metabolome represents the most precise and direct molecular expression of a phenotype. Combining metabolic information with proteome data, systems biology can draw an even more comprehensive picture of the biological processes. Here, we provide a review summarizing the results from human as well as animal studies analyzing metabolic and proteomic traits in different tissues for associations with anxiety. In addition, we give an overview of animal studies that applied a systems biology approach using metabolic as well as proteomic data to identify anxiety-related pathways.