This study aims to explore the longitudinal interrelationships among self-esteem, acculturation stress, and school adjustment among middle school students from multicultural families by employing an autoregressive lagged model to enhance the well-being of multicultural children and adolescents. This study analyzed the Multicultural Adolescent Panel Data (MAPS 1) covering the 4th to the 6th academic years of 1,316 middle school students from multicultural families. The results revealed that, first, the self-lagged effects of self-esteem, school adjustment, and acculturation stress were stable over time. Specifically, self-esteem, school adjustment, and acculturative stress at earlier time points significantly influenced these factors at later time points for both boys and girls. Second, a gender comparison of the cross-lagged effects revealed distinct patterns. For boys, there were significant reciprocal relationships between self-esteem and school adjustment, as well as between self-esteem and acculturation stress. Moreover, school adjustment significantly affected acculturation stress. For girls, earlier self-esteem influenced later acculturation stress, while prior school adjustment affected subsequent self-esteem. These findings highlight the importance of addressing self-esteem, school adjustment, and acculturation stress in supporting the well-being of adolescents from multicultural families. The implications for social welfare practices are discussed based on these results.