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Background Globally, children still face the challenge of delayed early development. The disparities in early childhood development (ECD) within economically developed areas remain unclear. Based on the analysis of the existing child health management system database, child healthcare professionals could quickly and conveniently confirm the supervision direction of ECD. Objective This study aimed to assess and compare ECD characteristics and influencing factors in economically developed megacities in China. Methods This is a retrospective cohort study. Participants included 13 436 children aged 0-3 years enrolled in the Child Health Management System from 2017 to 2020 in Shanghai and Shenzhen. Data on demographic information, birth status, and ECD characteristics were evaluated by child healthcare physicians. The all-round ECD indicators included physical development, gross motor development, and comprehensive cognitive, language, socio-emotional, and fine motor development. Descriptive statistics, univariate analysis, and multivariate analysis were used to analyze the ECD characteristics in Shanghai and Shenzhen and compare the consistency and difference between the two regions. Results Overall, among the 13 436 children, 10 890 (81.1%) were from Shanghai, and 2 546 (18.9%) were from Shenzhen. In terms of physical development, Shenzhen children were taller and heavier and had unclosed anterior fontanelle than Shanghai children (P<0.05). Only the Shanghai database covered the other dimensions of ECD. The results showed that the gross motor development and comprehensive cognitive, language, socio-emotional, and fine motor development of Shanghai children fell behind age-adjusted standards. Birth in summer or winter, birth height and weight, and premature delivery were common influencing factors for height development in both regions; Shanghai children's height development was mostly influenced by multiple births (β=-0.067), while premature delivery (β=0.094) was the most significant factor for Shenzhen children. Birth in winter, birth height, and premature delivery were common influencing factors for weight development in both regions (P<0.05); Shanghai children's weight development was especially influenced by multiple births (β=-0.070); while premature delivery (β=0.066) was the most significant factor for Shenzhen children. Anterior fontanel closure was influenced by father's occupation, birth weight, pregnancy times, and especially the summer season of birth (OR=2.104). The early motor development was influenced by foreign nationality, father's occupation, birth season, birth height, gestational week, and especially premature delivery (β=0.291). The comprehensive cognitive, language, social-emotional, and fine motor development was influenced by children's household registration type, mother's occupation, mother's age, birth season, birth height and weight, gestational week, pregnancy times, multiple births, and especially premature birth (β=0.310). Conclusion The ECD levels in megacities such as Shanghai and Shenzhen demonstrate notable variations; while the underlying mechanisms differ, the influencing factors share certain commonalities. Child healthcare professionals can increase the monitoring, intervention, and follow-up of children with the considerations of the following characteristics: parents' occupations, personnel category, mother's age, gestational week, and premature delivery. Early intervention during pregnancy and shortly after birth may reduce the potential adverse effects of risk factors.