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Abstract Background Drug-related problems (DRPs) are frequently observed in intensive care units, resulting in a higher occurrence of drug side effects and increased treatment expenses. This study aimed to assess the prevalence of DRPs in pediatric patients admitted to the most prominent surgical and medical pediatric intensive care units (PICUs) in southern Iran, given the susceptibility of children to the effects of DRPs. Method This cross-sectional study was conducted at Namazi Hospital, which is affiliated with Shiraz University of Medical Sciences in Shiraz, Iran, from June 2022 to March 2023. The research focused on identifying and detecting drug-related problems (DRPs) among pediatric patients during their hospital stays across three medical wards, two pediatric intensive care units, and a surgical intensive care unit. The identification process occurred concurrently with patient treatment and utilized the Pharmaceutical Care Network of Europe’s data collection form for DRPs version 8.01. Before any documentation, all cases were thoroughly reviewed and validated by a professional focus group. The data gathered were then statistically analyzed using SPSS to evaluate the study’s outcomes. Result During the study, 323 pediatric patients were involved, of whom 57% experienced at least one DRP. The primary issues identified during the study were suboptimal drug treatment, accounting for 41.13% of cases, followed by concerns related to treatment safety, which constituted 38.53% of cases. Drug-drug interactions were found to be the leading cause of DRPs, accounting for 36.26% of cases. Two significant factors associated with DRP occurrence were the number of prescribed drugs and the number of prescribed anticonvulsants. Out of all clinical pharmacist interventions, 97% were accepted. Conclusion Patients admitted to the PICUs experience a high occurrence of DRPs. It is essential to consider optimal dosage adjustment, particularly for pediatric patients with impaired kidney function.