Focal Cortical Dysplasia IIB (FCDIIB) represents a large variety of cortical malformations associated with abnormal cortical layering and appearance of dysmorphic neuronal elements, often occurring in the frontal cortex. FCDIIB is a common cause of pharmaco-resistant epilepsies and altered local neuronal activity has been reported in human FCDIIB tissue samples. Local cortical microcircuits are extensively modulated by monoaminergic axonal projections arising from the brain stem. Previous analysis of monoaminergic modulatory inputs in human FCDIIB biopsies suggested altered density and distribution of these monoaminergic axons. However, a systematic investigation is still pending. Here, we perform a comprehensive analysis of monoaminergic axonal projections, with a focus on dopaminergic (DA) innervation, in human FCDIIB biopsies and in the medial prefrontal cortex (mPFC) of FCDIIB mouse models (mTOR hyperactivation model) during juvenile and adult stages. Moreover, we analyze the expression of dopamine receptors Drd1 and Drd2 via multiplex fluorescent RNA in situ hybridization in human specimen and the mPFC of this mouse model. Our results suggest an altered lamination pattern of DA innervation in the FCDIIB area compared to the control area. In the mTOR hyperactivation mouse model, we observe a trend toward decreased innervation in adulthood. Drd1 and Drd2 mRNA receptors appear to be highly expressed in the dysmorphic neurons in human samples and mTOR-mutated cells in mice compared to normally-developed neurons. Overall, our results suggest potential alterations in DA neurotransmission in FCDIIB that may be important for understanding disease mechanisms of cortical malformations and epilepsy in FCDIIB.