Emotional and motivational processes are vital for functioning in everyday life and mental health. Dysregulations in these domains critically impede adaptive functioning and represent a transdiagnostic feature across major mental and neurological disorders. A significant proportion of individuals with pathological dysregulations in these domains do not adequately respond to the currently available interventions and thus integrated translational strategies that precisely determine the underlying brain systems and explore novel strategies to modulate the identified targets in humans are urgently needed. In the present talk I will outline synergistic strategies that aim at determining the brain basis of emotions via fMRI-based neural decoding (neuroaffective signatures), how these brain circuits can be modulated via targeting neuropeptide systems (Oxytocin, Angiotensin II) in humans, and discuss critical next steps in translating these approaches into clinical applications for brain-based disorders.