Neuromodulation of central and peripheral neural circuitry brings together neurobiologists and neural engineers to develop advanced neural interfaces to decode and recapitulate the information encoded in the nervous system. Dysfunctional neuronal networks contribute not only to the pathophysiology of neurological diseases, but also to numerous metabolic disorders. Many regions of the central nervous system (CNS), especially within the hypothalamus, regulate metabolism. Recent evidence has linked obesity and diabetes to hyperactive or dysregulated autonomic nervous system (ANS) activity. Neural regulation of metabolic functions provides access to control pathology through neuromodulation. Metabolism is defined as cellular events that involve catabolic and/or anabolic processes, including control of systemic metabolic functions, as well as cellular signaling pathways, such as cytokine release by immune cells. Therefore, neuromodulation to control metabolic functions can be used to target metabolic diseases, such as diabetes and chronic inflammatory diseases. Better understanding of neurometabolic circuitry will allow for targeted stimulation to modulate metabolic functions. Within the broad category of metabolic functions, cellular signaling, including the production and release of cytokines and other immunological processes, is regulated by both the CNS and ANS. Neural innervations of metabolic (e.g. pancreas) and immunologic (e.g. spleen) organs have been understood for over a century, however, it is only now becoming possible to decode the neuronal information to enable exogenous controls of these systems. Future interventions taking advantage of this progress will enable scientists, engineering and medical doctors to more effectively treat metabolic diseases.