Abstract Background The increasing worldwide prevalence of multidrug‐resistant (MDR) bacteria underscores the pressing demand for innovative therapeutic solutions. Ceftazidime‐avibactam (CAZ‐AVI) represents a promising new drug combination that has received approval for specific infection types. However, there is limited information regarding its application in pediatric patients. Methods This study investigates the effectiveness and adverse reactions associated with CAZ‐AVI treatment in pediatric patients with life‐threatening infections caused by MDR pathogens. The study was conducted at a tertiary children's hospital between December, 2021 and July, 2023. Results A total of 21 patients with life‐threatening infections caused by MDR pathogens were enrolled in the study. All patients had underlying medical conditions: 10 had cerebral palsy, four had congenital neurometabolic disease, two had Nieman–Pick disease, two had cystic fibrosis, two had primary immunodeficiency, and one had leukemia. Among these, 12 patients had tracheostomies. Eight patients received CAZ‐ AVI monotherapy, and 13 patients received combination therapy. Microbiological eradication was achieved in 18 patients (85.7%), and a clinical response was observed in 20 patients (95.2%). Two patients (9.5%) experienced relapse with the same bacteria. One patient developed anaphylaxis, and one patient had elevated creatine phosphokinase levels that normalized following discontinuation of treatment. One patient died during the study period due to gastrointestinal bleeding. Conclusions Ceftazidime‐avibactam may be a promising new drug option for the treatment of life‐threatening infections caused by MDR Gram‐negative microorganisms in pediatric patients. However, further studies with larger case series are needed to further evaluate the efficacy and safety of CAZ‐AVI in this population.