This review combines findings from 24 studies on SCN1A's role in TLE. The analysis shows that SCN1A mutations cause febrile seizures and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Specific mutations raised the risk of MTLE-HS in some groups, but did not affect the risk of febrile seizures. Cortical malformations like focal cortical dysplasia and periventricular nodular heterotopia are common co-diagnoses with SCN1A mutations. This complicates diagnosis and treatment of TLE. Altered splicing of SCN1A caused drug resistance. This shows the need for precision in targeting these mutations for treatment. Variants had diverse effects on treatment response and drug resistance. This was likely due to changes in NF-kB activity and sodium channel function. Carbamazepine significantly reduced seizures by lowering SCN1A expression in the hippocampus. Some mutations caused drug-resistant epilepsy in patients with hippocampal sclerosis. This highlights the need for personalized treatments.