Objective This study was undertaken to test whether lesions causing central poststroke pain (CPSP) are associated with a specific connectivity profile, whether these connections are associated with metabolic changes, and whether this network aligns with neuromodulation targets for pain. Methods Two independent lesion datasets were utilized: (1) subcortical lesions from published case reports and (2) thalamic lesions with metabolic imaging using 18F‐ fluorodeoxyglucose positron emission tomography–computed tomography. Functional connectivity between each lesion location and the rest of the brain was assessed using a normative connectome (n = 1,000), and connections specific to CPSP were identified. Metabolic changes specific to CPSP were also identified and related to differences in lesion connectivity. Therapeutic relevance of the network was explored by testing for alignment with existing brain stimulation data and by prospectively targeting the network with repetitive transcranial magnetic stimulation (rTMS) in 7 patients with CPSP. Results Lesion locations causing CPSP showed a specific pattern of brain connectivity that was consistent across two independent lesion datasets (spatial r = 0.82, p < 0.0001). Connectivity differences were correlated with postlesion metabolism ( r = −0.48, p < 0.001). The topography of this lesion‐based pain network aligned with variability in pain improvement across 12 prior neuromodulation targets and across 32 patients who received rTMS to primary motor cortex ( p < 0.05). Prospectively targeting this network with rTMS improved CPSP in 6 of 7 patients. Interpretation Lesions causing pain are connected to a specific brain network that shows metabolic abnormalities and promise as a neuromodulation target. ANN NEUROL 2022;92:834–845