Background/Objectives: Meropenem is a broad-spectrum antibiotic essential for treating resistant Gram-negative infections in pediatric patients. Current dosing recommendations may not consistently achieve optimal pharmacokinetic (PK) targets, especially in critically ill children. Methods: We conducted a retrospective cohort study at IRCCS Istituto Giannina Gaslini, analyzing 97 plasma levels from 86 pediatric patients (<18 years) hospitalized between January 2020 and December 2023 in the neonatal and pediatric intensive care unit. Patients receiving meropenem for proven or suspected infections were included. Demographic, clinical, and PK parameters were assessed, with a focus on trough concentrations (C_trough). Results: The median age was 25 months, with neonates representing 15.5% of cases. The median C_trough was 2.8 mg/L and was significantly higher in neonates (8.9 mg/L) compared to older patients (2.2 mg/L, p < 0.001). Only 27.8% of patients achieved the target C_trough of >8 mg/L, with estimated glomerular filtration rate (eGFR) being the primary factor influencing these levels. Patients with C_trough > 8 mg/L had a significantly lower eGFR (61 mL/min/1.73 m²) compared to those below this threshold (131 mL/min/1.73 m², p = 0.001). Conclusions: The current meropenem dosing regimen may not reliably meet PK targets in critically ill pediatric patients, particularly those with augmented renal clearance or when treating pathogens with increased meropenem MIC. Our findings suggest that increased dosages and prolonged infusion times may be necessary to optimize therapeutic efficacy against resistant Gram-negative bacteria in this vulnerable population. Further studies are needed to refine dosing strategies and improve patient outcomes.