Abstract: Objective To investigate the clinical characteristics of drug-resistant Mycoplasma pneumoniae pneumonia (MPP) in children. Methods Retrospective analysis was conducted on the clinical data of 210 children with drug-resistant MPP who were admitted to the Children's Medical Center, the Second Affiliated Hospital of Nanjing Medical University from January to December 2024. Results In 2024, a total of 210 cases of drug-resistant MPP were identified, accounting for 25.00% of all hospitalized MPP cases during the same period. The percentage of girls with drug-resistant MPP was higher than that of boys (χ²=7.914, P=0.005). Among the 210 children, 32 were aged 0-3 years, 70 were >3-7 years, and 108 were >7 years; the percentage of drug-resistant cases increased with age, with statistical differences (χ²=19.356, P<0.001). The distribution of resistant MP infections varied across seasons, also showing statistical significance (χ²=15.277, P<0.05). The incidence of major clinical symptoms (duration of fever, fever intensity, cough, and pulmonary rales) did not differ significantly among age groups (P>0.05), but the proportion of high fever increased in children >3 years (P<0.05). Some children developed extrapulmonary complications, mainly myocardial damage and skin/mucosal damage. There were no significant differences in C-reactive protein, lactate dehydrogenase, procalcitonin, or erythrocyte sedimentation rate among age groups (P>0.05). However, the incidence of pulmonary complications increased significantly with age (χ²=8.160, P<0.05). Among co-infections, Epstein-Barr virus and influenza A/B virus were the main viral pathogens, while Haemophilus influenzae and Streptococcus pneumoniae were the main bacterial pathogens. Most children showed good outcomes after treatment with potent antibiotics combined with corticosteroids or bronchoscopy. Conclusions Drug-resistant MPP in children shows differences in sex, age, and seasonal distribution. Clinical manifestations and laboratory findings are not age-dependent, but older children often present with more severe imaging findings. Myocardial and skin/mucosal damage are the main extrapulmonary complications, and some children experience bacterial or viral co-infections. Rational antibiotic selection and the use of bronchoscopy play important roles in the treatment of drug-resistant MPP.