This proposal will ultimately contribute important foundational knowledge in the following areas: (1) neurodevelopmental outcomes of children exposed to drugs in the prenatal stage that may be dependent on the nature, timing, and dosage of environmental insult in addition to the child’s neurobiological-genetic- genomic factors and resilience/reserve; (2) timing of opportunities and modifiable targets; and (3) assessing underlying mechanisms of substance use disorder and withdrawal symptom across mother-infant/child generations. Ultimately, research such as ours may help to optimize circuit-based precision interventions in these vulnerable children that have rapidly increased in recent years.