BACKGROUND: Healthcare professionals play an essential role in reporting adverse drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported by healthcare professionals remain low. OBJECTIVE: The aim of this systematic review was to investigate healthcare professionals' knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction reporting, explore the causes of the underreporting issue, and provide improvement strategies. METHODS: This systematic review was conducted using four electronic databases for original papers, including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January 2012 to 31st December 2022 were selected. The following terms were used in the search: "awareness", "knowledge", "adverse drug reaction", "pharmacovigilance", "healthcare professional", and "underreporting factor". Articles were chosen, extracted, and reviewed by the two authors. RESULTS: Twenty-five studies were selected for systematic review. This review found that 24.8%-73.33% of healthcare professionals were unaware of the National Pharmacovigilance Center. Around 20%-95.7% of healthcare professionals have a positive attitude toward pharmacovigilance and adverse drug reaction reporting, while 12%-60.8% of healthcare professionals have experience reporting any adverse drug reaction in their practice. The most frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge regarding what, when, and to whom to report. CONCLUSION: Underreporting issues require immediate attention among healthcare professionals due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction reporting. Educational and training program interventions have been suggested by most studies to address these issues.