Teacher stress significantly challenges teachers’ health, teaching quality, and students’ motivation and achievement. Thus, it is crucial to identify factors that effectively prevent it. Using a LASSO regression approach, we examined which factors predict teachers’ psychological strain and allostatic load over two years. The study included 42 teachers (28 female,Mage = 39.66,SD= 11.99) and three measurement time points: At baseline, we assessed teachers’ (a) self-reports (i.e., on personality, coping styles, and psychological strain), (b) behavioral data (i.e., videotaped lessons), and (c) allostatic load (i.e., body mass index, blood pressure, and hair cortisol concentration). At 1- and 2-year follow-ups, psychological strain and allostatic load biomarkers were reassessed. Neuroticism and perceived student disruptions at baseline emerged as the most significant risk factors regarding teachers’ psychological strain two years later, while a positive core self-evaluation was the most important protective factor. Perceived support from other teachers and the school administration as well as adaptive coping styles were protective factors against allostatic load after two years. The findings suggest that teachers’ psychological strain and allostatic load do not primarily originate from objective classroom conditions but are attributable to teachers’ idiosyncratic perception of this environment through the lens of personality and coping strategies.