Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and how they affect cell-type-specific transcriptional programs remains unknown. To address this question, here we combined single-nucleus genotyping and transcriptomics in morphologically-identified cells using surgical cortical samples from genetically-characterized FCDII patients. Mutations were predominantly detected in glutamatergic neurons and astrocytes and only a small fraction of mutated cells exhibited cytomegalic features, revealing incomplete penetrance of FCDII-causing mutations. Moreover, we identified cell-type-specific transcriptional dysregulations in both mutated and non-mutated FCDII cells, including synapse and neurodevelopment-related pathways, that may account for epilepsy, and dysregulation of mitochondrial metabolism pathways in cytomegalic cells. Together, these findings reveal cell-autonomous and non-cell-autonomous mechanisms at play in FCDII, towards the development of precision therapies for this disorder.