Background: Adverse drug reactions (ADRs) are one of the leading causes of mortality and morbidity. Avoiding adverse reactions requires comprehensive knowledge about how they can be monitored, controlled, and reported. Objectives: The current study aimed to evaluate the knowledge, attitude, practices, and perceptions of the health care professionals concerning the adverse drug reactions monitoring and reporting in Lahore, Pakistan. Methods: A prospective cross-sectional study was conducted in Lahore, Pakistan, from October 2018 to December 2018. Descriptive statistics were obtained and the Pearson chi-square test was used to analyze the association between categorical variables. Results: In total, 150 pharmacists, physicians, and nurses were approached, that 40, 39, and 46 of them responded, respectively. Almost 95% pharmacists, 17.3% of nurses, and 58.9% of physicians correctly defined the “pharmacovigilance”, while 70, 10, and 30.5%, respectively, defined ADRs correctly. The current study revealed that 87% of pharmacists, 82.5% of physicians, and 82.6% of nurses had a history of identifying ADR in patients. Out of which only 52, 41, and 19% of pharmacists, physicians, and nurses had a history of reporting adverse drug reactions, respectively. Conclusions: This study revealed inadequate knowledge of health care professionals. Most healthcare professionals were motivated to report identified ADRs. However, the responsibility lies with the governing authorities to provide them with a suitably efficient platform to practice proper ADR reporting and monitoring. Educational campaigns and training, financial incentives, and simplification of the reporting process might change the levels of knowledge and attitude.