Objective: Academic stress is associated with mental health disorders, notably depression and anxiety among students. Mitigating stress can decrease the incidence of mental health disorders and improve student well-being. This study explored factors influencing academic stress among secondary school students in Vietnam.Materials and Methods: A three-year longitudinal study was conducted using a self-reported questionnaire with 611 students from four secondary schools in Hue City, Vietnam. Academic stress was evaluated using the Educational Stress Scale for Adolescents (ESSA). Family factors, including the number of siblings and parental educational levels; lifestyle factors, including physical activity and sleep; and academic factors, including grade point average and attending extra classes were evaluated. Linear regression models were used to analyze the associations between the ESSA scores at follow-up and family, lifestyle, and academic factors at baseline.Results: A total of 341 students completed both the baseline and follow-up surveys and answered the questions required for this analysis. The mean ESSA score of 341 students increased from 46.4 ± 7.6 (mean ± SD) to 53.5 ± 10.8, from 2018 to 2021. The multivariate model revealed that the number of siblings, higher father’s educational attainment level, female gender, lower academic scores, and attending extra classes were associated with overall academic stress. In contrast, no associations were observed between the variables of lifestyle, parental concentration, and parental acceptance and overall academic stress.Conclusion: The findings highlight the impact of family factors and study workload on academic stress, emphasizing the need for proper care from family and school to reduce or prevent student academic stress and provide them with a comfortable and healthy learning environment.