Background: Health care workers are respected in every society and have a strong influence on the behaviour of the community. In order to reduce the shisha dependence in the Pakistani population, it is necessary to evaluate the perspective of future doctors and pharmacists regarding this addiction as they become role models for the future generations. Objective: The aim is to compare the knowledge, attitudes, and practices of shisha use among medical students and pharmacy students in order to assess their support in the anti-shisha campaigns of Pakistan. Methodology: Cross sectional study was performed in four major medical universities of Karachi, Pakistan through a modification of the WHO global health survey questionnaire. Result: 398 medical students and 470 pharmacy students were included in the study which showed that currently 9.6% pharmacy students and 4.8% medical students used shisha daily (p = 0.000). Pharmacy students started shisha use in less than 15 years of age while this number was 29.5% among medical students (P = 0.000). Moreover, 44.6% pharmacy students and 50% medical students were not planning to quit this addiction within the next six months. 14% of pharmacy students and 20.4% in medical students (P = 0.002) were unaware that passive smoking caused lung cancer, while 23.4% pharmacy students and 33.5% medical students rejected it as cause of heart diseases (p = 0.006). Conclusion: A significant number of medical and pharmacy students were unaware about some of the serious consequences of shisha smoking. Therefore, both groups of students need to be educated about the health hazards of shisha use, in order to control this growing menace.