Background & Objective: Mental distress, such as anxiety and depression, are important components that affect educational achievement. This study aimed to examine the mediating role of anxiety and depression in the relationship between academic satisfaction and academic performance among bachelor's and master's nursing students. Materials & Methods: This is a cross-sectional study that utilized a structural equation model. Sampling was conducted using a two-stage cluster sampling method, considering the inclusion and exclusion criteria for 1,695 bachelor's and master's nursing students from February 11 to November 30, 2019. Data were collected using four questionnaires, namely a demographics survey, the Spielberger State-Trait Anxiety Inventory (STAI), the Patient Health Questionnaire-9 (PHQ-9), and the Academic Satisfaction Scale. Data analysis was conducted using SPSS 26.0 and the macro PROCESS model 6 to evaluate the mediating effects of depression and anxiety simultaneously. A p-value of less than 0.05 was considered statistically significant. Results: This study demonstrated that the direct effect of nursing students' academic satisfaction significantly correlated with their academic performance. Additionally, the relationship between nursing students' academic satisfaction and academic performance was significantly mediated, both separately and simultaneously, by their levels of depression and anxiety (β = 0.0005, CI = 0.0001 to 0.001). Conclusion: Considering the importance of academic satisfaction and performance of nursing students, as well as the adverse effects of anxiety and depression on these variables, the implication of suitable strategies is essential for preventing academic burnout. Therefore, educational system authorities are advised to prioritize students' well-being to prevent future negative consequences, especially in their professional roles.