Background <p>Burnout is a work-related syndrome characterized by emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA), and is highly prevalent among medical trainees, particularly in resource-limited settings. This study aimed to assess the prevalence and associated factors of burnout among medical interns at a tertiary hospital in Ethiopia.</p> Methods <p>A cross-sectional survey of 112 medical interns at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia, was conducted between August and September 2023. Burnout was assessed using the Maslach Burnout Inventory (MBI). Sociodemographic, personal, and work-related variables were collected. Ordinal logistic regression was used to identify independent associations between intern characteristics and burnout domains.</p> Results <p>High levels of EE (82.1%) and DP (79.5%) were observed, while low PA was found in 12.5% of interns. Overall, 50% met criteria for burnout in at least one MBI dimension. Intention to emigrate was independently associated with high EE (adjusted odds ratio [AOR] 15.05, 95% confidence interval [CI]: 0.77–29.0, <i>p</i> = 0.08), though this was not statistically significant as the confidence interval included 1. Lack of a definite career plan was associated with higher EE as well (AOR 4.93, 95% CI: 1.12–21.56, <i>p</i> = 0.03). Male gender significantly predicted higher DP (AOR 4.11, 95% CI: 2.38–8.42, <i>p</i> = 0.001). Sleep disturbance and frequent duty shifts were also prevalent and correlated with increased burnout.</p> Conclusion <p>Burnout is a significant problem among Ethiopian medical interns, with particularly high rates of EE and DP, and notable but lower rates of low PA. Key factors include sleep disruption, career uncertainty, and intention to emigrate. Targeted interventions to support intern well-being, clarify career pathways, and reduce job-related stress are urgently needed.</p>