The global prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia infections, particularly in children, is on the rise. It is imperative to assess the clinical efficacies of alternative antibiotics such as tetracyclines to ensure effective treatment, mitigate antibiotic resistance, enhance clinical outcomes, and minimize the spread of resistant strains among MRMP-infected children. The objective of this study was to compare the therapeutic efficacies of macrolides and tetracyclines in treating MRMP pneumonia in children. We systematically searched the literature to identify comparative studies that examined the clinical outcomes of macrolide and tetracycline antibiotics in children with MRMP pneumonia. We conducted a meta-analysis of the mean duration of fever, hospital stay duration, therapeutic efficacies, and time to defervescence to compare macrolides and tetracyclines. Eleven studies involving 1143 patients compared the clinical efficacies of macrolides and tetracyclines in children with MRMP pneumonia. The studies were conducted in China, Japan, and Korea, and the outcomes of febrile days, hospital stay duration, therapeutic efficacy, and time to defervescence were analyzed. The macrolides studied were azithromycin and clarithromycin, whereas the tetracyclines included minocycline and doxycycline. The pooled estimate of 5 studies showed that the mean duration of febrile days and hospital stay was longer in the macrolides group than tetracycline group [weighted mean difference = 1.64 days, 95% confidence interval (CI): 0.68-2.59, weighted mean difference = 1.22 days, 95% CI: 0.82-1.62, respectively]. The therapeutic efficacy was significantly lower in the macrolide group than in the tetracycline group (odds ratio: 0.33, 95% CI: 0.20-0.57). The clinical efficacy of tetracycline treatment was superior to that of macrolide treatment in children with MRMP pneumonia. However, further research is required to validate these findings and inform evidence-based clinical practice guidelines.