In recent years, the incidence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia has markedly increased across East Asia, especially in China, Japan, and South Korea, presenting considerable challenges for clinical management. We systematically reviewed and conducted a meta-analysis on the resistance rate, clinical characteristics, and associated factors of MRMP, thereby establishing a foundation for early clinical identification and optimization of treatment strategies. In accordance with the PRISMA 2020 reporting guidelines, six databases including PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang Data were systematically searched for relevant literature up to October 31, 2024. Studies explicitly reporting the clinical characteristics of both MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia patients were included, with the population restricted to children. Pooled odds ratio (OR) and mean difference (MD), along with 95% confidence intervals, were calculated using inverse-variance weighting. A significance threshold was set at p < 0.05, and meta-analysis was performed using software such as RevMan, Stata, and R Studio. A total of 65 studies encompassing 20,141 patients were included in this analysis. The meta-analysis revealed that MRMP showed high resistance in East Asia compared to lower resistance in other regions. The overall resistance rate was 61% (95% CI: 54%, 68%), exhibiting notable regional variation. Elevated resistance rates were noted in East Asian countries, specifically China, Japan, and South Korea, reported at 68% (95% CI: 63%, 73%), 61% (95% CI: 43%, 80%), and 63% (95% CI: 42%, 85%), respectively. MRMP resistance was significantly associated with prolonged fever duration (MD: 1.97, 95% CI: 1.10, 2.84), extended hospitalization (MD: 1.96, 95% CI: 1.39, 2.54), elevated log MP-DNA levels (MD: 2.79, 95% CI: 1.54, 4.04), increased proportions of severe (OR: 2.45, 95% CI: 1.75, 3.44) cases and refractory (OR: 3.25, 95% CI: 1.47, 7.17) cases, and the occurrence of complications, particularly intrapulmonary manifestations including pulmonary consolidations (OR: 1.43, 95% CI: 1.14, 1.78), pleural effusions (OR: 2.11, 95% CI: 1.28, 3.49), lobar lesions (OR: 2.03, 95% CI: 1.03, 4.00), mucus plugs (OR: 4.63, 95% CI: 1.66, 12.94), and necrotizing pneumonia (OR: 2.49, 95% CI: 1.19, 5.24), alongside extrapulmonary involvement (OR: 3.08, 95% CI: 2.49, 3.82). No significant differences were observed in peak body temperature (MD: 0.05, 95% CI: -0.11, 0.20) or inflammatory markers including white blood cell count (WBC, MD: 0.28, 95% CI: -0.38, 0.94), C-reactive protein (CRP, MD: 0.71, 95% CI: -2.16, 3.58), Procalcitonin (PCT, MD: -0.11, 95% CI: -0.27, 0.05) and lactate dehydrogenase (LDH, MD: 3.80, 95% CI: -22.92, 30.52). The high resistance rate may be associated with environmental pressure stemming from the widespread use of macrolide antibiotics and increased genetic mutations due to the extensive spread of MP. The observed increase in severe cases, refractory cases, and complications associated with MRMP may be attributed to prolonged colonization resulting from ineffective anti-Mycoplasma pneumoniae treatment, rather than to enhanced virulence or a more severe cytokine storm. PROSPERO registration number CRD42024550871.