In the realm of medical education, clinical internship represents a pivotal phase where theoretical knowledge must be practically applied amidst real-world patient care, often leading to heightened stress and anxiety among interns. This transitional challenge is particularly acute for tuberculosis (TB) clinical interns, requiring innovative teaching methodologies. Therefore, we aim to evaluate the efficacy of integrating clinical pathway instruction with scenario-based simulation teaching in alleviating psychological stress and anxiety among TB clinical trainees. Data extraction from electronic health and educational evaluation records spanned September 2020 to September 2022, focusing on TB clinical interns. The investigation centered on 2 principal teaching methodologies used during training: the combination of clinical pathway and scenario simulation approaches. Standardized instruments quantified psychological stress and anxiety at 3 intervals - pre-teaching, post-teaching, and a 6-month follow-up. The study encompassed 70 TB clinical interns, allocating 34 to a combined teaching approach integrating clinical pathways and scenario simulations, while 36 underwent conventional teaching methodologies. Post-intervention assessments revealed significant reduction in psychological stress levels among those subjected to the combined methods (t = 2.522, P = .014). This difference was further magnified at the 6-month follow-up, with the combined teaching method group demonstrating markedly lower psychological stress levels (t = 3.54, P < .001). Also, immediately following the intervention, the combined method group experienced significantly lesser anxiety (t = 2.278, P = .026), and the beneficial effect endured through the 6-month mark (t = 2.41, P = .019). Combining clinical pathway teaching method and scenario simulation teaching method are associated with reduced psychological stress and anxiety levels among TB clinical interns.