Prurigo nodularis (PN) is a chronic pruritic inflammatory skin condition characterized by nodular skin lesions in a typical distribution pattern caused by various dermatological and/or non-dermatological conditions. In recent years, significant advances have been made in the understanding of the cutaneous pathophysiology of PN resulting in novel treatment options such as Interleukin-4, -13, -17, -31- or Januskinase inhibitors. However, many aspects of the neurophysiology are largely unknown, including the processing in the central structural and functional network involved in PN. Functional neuroimaging allows non-invasive assessment of brain function and structure. Due to its high spatial resolution and temporal precision, functional magnetic resonance imaging (fMRI) has proven to be a suitable method for exploring neural mechanisms and assessing pharmacological effects in dermatological research. In this systematic review, the current knowledge of fMRI in the context of PN and its centrally active treatment options is summarized.