Objectives Burnout is a psychophysiological syndrome, consisting of a triad of emotional and physical exhaustion, exhibition of impersonal attitude and loss of a sense of achievement for oneself. This study aimed to pinpoint its risk factors, measure its current prevalence in medical students of Karachi, Pakistan and accentuate the areas of focus to benefit the primary care-oriented community as a whole. Methods This cross-sectional study included responses from 600 medical students in Karachi (third to final year). A self-administered questionnaire using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), multi-dimensional mood state questionnaire and perceived stress scale was used, along with a section about burnout prevention assessment. Data were analyzed using SPSS version 24.0 (IBM Corp., Armonk, NY) and chi-square tests used to find significant associations. Results One-fifth (n=109, 18.2%) of our subjects were burned out. The syndrome was significantly observed in those who operated on insufficient sleep (p-value 0.028) and in those having anger management issues and non-dominating temperaments (p-value 0.05). Furthermore, it was statistically significant in those who gave up easily, in those who had no hobbies and had no time to exercise and pray (p-value <0.05). It was more prevalent in pupils of private medical colleges whereas two of its three constitutive factors, Emotional Exhaustion (p-value 0.03) and Personal Achievement (p-value <0.001) were significantly higher in pupils of public sector universities.  Conclusion The deleterious repercussions of burnout syndrome warrant the need for extensive efforts towards the propagation of its awareness.