Self-esteem and personality traits play a crucial role in determining the psychological health and academic performance of medical students. This cross-sectional study examines the relationship between self-esteem and the Big Five personality traits in medical students in Central Park Medical College Lahore Pakistan and sheds light on how these factors work together in a high-stress environment. A total of 300 medical students used validated self-report measures, including the Rosenberg Self-Esteem Scale and Big Five Inventory. The preliminary findings suggest that the levels of self-esteem are positively related to extraversion (p<0.01), agreeableness (p<0.05), and conscientiousness (p<0.01); however, neuroticism has a very strong negative association (p<0.001). A strong predictive ability of personality traits on self-esteem could also be determined, with personality traits accounting for 45% of the variance in the self-esteem score. These results indicate the importance of developing personality traits in medical students to maintain self-esteem. The significance of this study is that it explores one specific aspect of the impact of certain personality dimensions on self-esteem levels, which may help develop new approaches in medical education.