Developmental epilepsy-dyskinetic encephalopathy (DEDE) is a collective term for a group of genetic disorders characterized by refractory involuntary (hyperkinetic) movements, often accompanied by severe drug-resistant epilepsy and developmental delay or regression, with a high rate of genetic diagnosis. Driven by multidisciplinary technologies—particularly next-generation sequencing—epilepsy genetics has made significant strides. This review delineates the landscape of genetic etiologies, clinical presentations and advancements in precision medicine for developmental epilepsy-dyskinetic encephalopathy. The manuscript focuses on how specific pathogenic genes disrupt core neurobiological processes, including ion channel function and neurotransmitter metabolism. It summarizes personalized treatment approaches already applied to certain monogenic epilepsies, heralding the era of precision medicine.