Chronic pain affects almost 20% of the European adult population and it significantly reduces patients’ quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.