Background <p>Self-medication, the use of medications without professional consultation, is prevalent among medical students and poses risks such as drug misuse and delayed diagnosis. This study examined the roles of stress, self-efficacy, and health literacy in self-medication behaviours among undergraduate medical students in Pakistan.</p> Methods <p>A cross-sectional study was conducted from April to May 2025 at Nowshehra Medical College, involving 241 students (158 females and 83 males) selected through a convenience sampling method. A self-modified structured questionnaire was used to assess health literacy (nine items), self-efficacy (six items), stress (ten items), and self-medication behaviour. Data were analyzed using SPSS v30.0, employing t-tests to compare sex differences and binary logistic regression to identify predictors of the outcome. Ethical approval was obtained (Ref. 30/ERB/NMC).</p> Results <p>No sex differences were found in health literacy (<i>p</i> = 0.630) or self-efficacy (<i>p</i> = 0.156), but females reported higher stress (<i>p</i> &lt; 0.001, Cohen’s d = -0.59). Logistic regression models indicated that health literacy factors were not significant predictors (<i>p</i> &gt; 0.05). However, significant predictors included reliance on past experiences (OR = 1.823, <i>p</i> = 0.003) and health-related stress (OR = 1.607, <i>p</i> = 0.007), while safe self-medication practices were protective (OR = 0.679, <i>p</i> = 0.027). The overall model explained 18.5% of the variance (Nagelkerke R² = 0.185) but had low classification accuracy (47.9–49.2%). Visualisations, including bar charts, ROC curves, box plots, and heatmaps, highlighted the stress disparities and predictor strengths.</p> Conclusion <p>Unsupervised medication use and stress drive self-medication among medical students. Targeted interventions should promote safe practices, address gender-specific stressors, and enhance health literacy to mitigate risks.</p>