Developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS) is a childhood-onset epilepsy syndrome characterized by cognitive regression or stagnation and marked activation of epileptiform activity during sleep. DEE-SWAS refers to cases with pre-existing neurodevelopmental disorders, whereas EE-SWAS is applied when development was initially normal before the onset of epileptic encephalopathy. This syndrome comprises approximately 0.2%-1.3% of all pediatric epilepsies. D/EE-SWAS etiology includes structural anomalies and autoimmune and genetic causes, although etiology frequently remains unknown. The active epileptic process in a developing brain results in impairment of cognitive functions and behavior. For this reason, early recognition of the electroclinical syndrome and treatment initiation is extremely relevant for the long-term cognitive outcome. Typically, the available therapeutic strategies consisted of low-quality evidence and limited effectiveness, such as combinations of antiseizure medications and steroids, which were based on syndromic diagnoses rather than etiology-driven hypotheses. Over the last years, treatment has been shifting toward precision medicine approaches, with an increasing proportion of genetic diagnosis, new evidence supporting the efficacy of the surgical option in selected patients, and specific targeted treatments, such as l-serine in GRIN-related disorders. Additionally, this coexists with ongoing clinical trials with syndrome-specific design for D/EE-SWAS. This narrative review aims to summarize the evidence on treatments for D/EE-SWAS, provide updates on drugs currently in development, and explore precision medicine approaches for this syndrome, seeking to combine both syndrome- and etiology-driven treatment strategies.