The primary somatosensory cortex (SI) is a critical part of the neural substrate underlying interindividual differences in pain sensitivity. Here, we investigated whether resting-state functional connectivity, gray matter density (GMD), and GABA and Glx (glutamate and glutamine) levels of the sensorimotor cortices were related to pain thresholds and whether such imaging measures could predict high and low pain sensitivity. Functional, structural, and spectroscopic magnetic resonance data were obtained from 48 healthy participants together with pain thresholds of the right index finger. Left and right sensorimotor networks (SMN) were extracted by means of independent component analysis, and GMD was measured within the combined SMN by means of voxel-based morphometry. Spectroscopic data were acquired from the bilateral sensorimotor cortices. Within the left SMN, functional connectivity to the right SI correlated positively with pain thresholds. In addition, GMD in the left SI and the GABA laterality index correlated positively with pain thresholds. A positive correlation was also found between the GABA laterality index and the left SMN connectivity to the right SI. Finally, the above mentioned functional connectivity and GMD measures could correctly predict high and low pain sensitivity in 83.7% of the study population. In summary, we showed that interindividual differences in pain sensitivity were related to the resting-state functional connectivity, interhemispheric GABA tone, and GMD of the sensorimotor cortices. Furthermore, high and low pain sensitivity could be predicted with high accuracy using imaging measures from the primary sensorimotor cortices.