Background: Due to the inflating prices of pharmaceutical products and services, medical burdens on patients and governments have increased. Pharmacoeconomics can assist decision-makers in allocating limited resources appropriately and utilizing cost-effective methods to improve patient care while reducing costs. However, pharmacoeconomics has still not been incorporated completely into practice.Objective: The aim of this cross-sectional study was to assess pharmacists' awareness, knowledge, and attitudes regarding pharmacoeconomics in the Al-Madinah Al-Munawara region in Saudi Arabia and to find interventions to improve the application of pharmacoeconomics in clinical practice. Methods: A validated questionnaire was used to collect demographic information and responses for the measures of awareness, knowledge, and attitudes about pharmacoeconomics. It was distributed among pharmacists of different nationalities, levels of education, degrees, and organizations in different cities in the Al-Madinah Al-Munawara region. Results: After applying the inclusion and exclusion criteria, 182 pharmacists' responses were included in the final analysis. The results showed suboptimal awareness (mean score = 1.95 out of 4) and knowledge (mean score = 1.62 out of 7) about pharmacoeconomics. However, 93% of the participants thought that applying pharmacoeconomics would improve the healthcare system. Conclusion: Pharmacists' awareness and knowledge of pharmacoeconomics are suboptimal. Policy implementation in healthcare organizations, addition of pharmacoeconomics courses in curricula, continuous medical education, encouraging self-involvement, and interest in the subject, will enhance their understanding. These would also expand the application of pharmacoeconomics in healthcare organizations and improve patient care and the utilization of healthcare resources, as well as reduce the total healthcare costs.