Natural rewards such as erotic stimuli activate common neural pathways with monetary rewards. In human studies, the manipulation of dopamine and serotonin play an important role in the processing of monetary rewards with less understood on its role on erotic stimuli. In this study, we investigate the neuromodulatory effects of dopaminergic and serotonergic transmission in the processing of erotic versus monetary visual stimuli. We scanned one hundred and two (N = 102) healthy volunteers using functional magnetic resonance imaging while performing a modified version of the well validated monetary incentive delay task consisting of erotic, monetary and neutral visual stimuli. We show a role for enhanced central dopamine and lowered central serotonin levels in increasing activity in the right caudate and left anterior insula during anticipation of erotic relative to monetary rewards in healthy controls. We further show differential activation in the anticipation of natural versus monetary rewards with the former associated with ventromesial and dorsomesial activity and the latter with dorsal cingulate, striatal and anterior insular activity. These findings are consistent with preclinical and clinical findings of a role for dopaminergic and serotonergic mechanisms in the processing of natural rewards. Our study provides further insights into the neural substrates underlying reward processing for natural primary erotic rewards and yields importance for the neurochemical systems of addictive disorders including gambling disorder.