Background: Responses to invasive neuromodulation therapy for chronic pain are highly variable after several months of sustained treatment, with some experiencing a complete loss of therapeutic effect. We sought to assess whether functional neuroimaging can provide a biomarker for treatment success and whether these biomarkers offer value in predicting treatment response. Methods: We searched Ovid MEDLINE and EMBASE from 1967 to 2022, including prospective studies correlating functional neuroimaging signatures with treatment response after surgical implantation. Results: After considering 355 studies for initial review, 22 studies were included. While there was significant heterogeneity in experimental design, preliminary findings suggest that differential regional cortical activation profiles and signatures can be employed to differentiate good from poor therapeutic responders. Three studies correlated pre-operative functional imaging with treatment effects post-implantation. For example, baseline activation patterns of specific brain regions on functional imaging modalities such as 11C-diprenorphrine PET and Tc-99m-SPECT significantly correlated with therapeutic response to motor cortex stimulation, and spinal cord stimulation (SCS), respectively. Conclusions: The included studies demonstrate the potential for functional imaging to predict the likelihood of successful neuromodulation treatment. The concept is relatively unexplored in the literature and could benefit from more studies with larger sample sizes to confirm clinical utility.