Background <p>Success in STEM subjects requires students to be inquisitive and willing to invest sustained efforts in learning. Curiosity and persistence, in particular, emerge as two pillars of STEM achievement. However, some studies have observed potential drawbacks of curiosity and persistence, indicating their intricate dynamics on STEM achievement that cannot be captured by traditional linear analyses. This study examined the linear and non-linear roles of curiosity and persistence alongside their interplay in predicting later STEM achievement, and further explored age-related heterogeneity. Response surface analysis was applied to a one-year longitudinal dataset from the United States (<i>N</i> = 4199; 49.1% female; 58.5% White).</p> Result <p>After controlling for demographic factors and prior academic achievement, (1) persistence emerged as the prominent predictor of mathematics and science achievement, (2) however, the positive effect of persistence on science became negative when curiosity level was low, and vice versa; and (3) non-linear effects and synergistic interactions of these two factors were more pronounced in both subjects among adolescents in 6–9th grades than in 10–12th grades.</p> Implications <p>Findings suggest that imbalances between curiosity and persistence may contribute to adverse STEM learning outcomes, underscoring the importance of fostering both factors in a balanced manner, especially during early adolescence.</p>