Objectives:To assess the level of burnout dimensions and investigate their correlation with substance abuse among undergraduate medical students at Taibah University in Al-Madinah Al-Munawarah, Saudi Arabia. Methods: This was an analytical study conducted at Taibah University, Al-Madinah, from January 2021 to July 2021. A self-administered questionnaire consisted of two sections. The first section identified the socio-demographic and personal characteristics of the participants. The second section presented the Maslach Burnout Inventory-Student Survey (MBI-SS). SPSS v26 was used for data analysis. Results:Of the 534 participants, 53.9% were females. The students mean (SD) age was 21.4 (1.59) years. Findings showed that 6% of the medical students had once used one or more types of substances, of which the majority (53.3%) used sleeping pills or sedatives. The average emotional exhaustion mean score of students in the survey population was 3.65 (1.46) out of 5. The students perceived emotional exhaustion scores were correlated significantly and positively with the total number of abused substances, p<0.050. The medical students total number of substance-used materials correlated significantly but negatively with their sense of personal study effectiveness, p<0.050. Students who had a positive history of substance use showed significantly higher cynicism (M=3.88) compared to students who had never abused substances (M=3.00) on average, p<0.001. Conclusion:Medical students at Taibah University demonstrated higher mean scores for emotional exhaustion and cynicism but a lower mean score for personal effectiveness. The students top burnout indicator was emotional exhaustion, followed by personal efficacy and cynicism.