Epilepsy is a chronic neurological disease of the brain. Over 20 antiseizure medications are available on the market, but a third of patients still have drug-resistant epilepsy. This study was designed to assess the impact of the demographic and clinical characteristics of epileptic children on their likelihood of developing drug resistance. This study was a multicenter, hospital-based, cross-sectional, case-control study of pediatric patients diagnosed with epilepsy in Jeddah, Saudi Arabia. The study included 101 children with epilepsy. Fifty-six patients showed good response to antiseizure medications (ASMs), and forty-five patients had a poor response. A statistically significant good response to ASMs was reported among younger patients, those who did not report parental consanguinity, those who did not have a family history of epilepsy, and those diagnosed with partial seizures, with no reported adverse effects. The levetiracetam regimen was statistically significant regarding the responsiveness to ASMs. Patients on a monotherapy regimen elicited a significantly better response to levetiracetam than patients on polytherapy ( < 0.001). No significant association was found between the response to ASMs and the sex, nationality, body mass index, complete blood count, or vitamin B12 level. In conclusion, the ASM response in epileptic patients can be predicted by knowing the patient's demographic and epileptic history. However, the complete blood count and vitamin B12 level failed to predict patients' response to ASMs.