Abstract Body (Do not enter title and authors here): Background: Betablockers including Metoprolol are commonly used to treat hypertension but have adverse drug responses like bradycardia and hypotension. Genetic polymorphism in cytochrome P450 2D6 is responsible for interpatient differences in drug response because this enzyme plays an important role in metabolizing metoprolol. There are pharmacogenomic guidelines available for treatment of heart failure, but not much information exists regarding patients with hypertension. Therefore, this study aims to investigates CYP2D6 genotype–metoprolol–ADR relationships in hypertensive patients to inform precision pharmacovigilance and develop AI pharmacovigilance system. Methods: We retrospectively analyzed Individual Case Safety Reports (ICSRs) from the FDA Adverse Event Reporting System (FAERS) from January 1997 to March 2025. We used filter such as reports with hypertension as the primary indication for metoprolol. Gene–drug–ADR associations were extracted from PharmGKB, focusing on CYP2D6 alleles with Level 1A & Level 3 evidence. We categorised ADRs using MedDRA terms; serious events involved hospitalization, life-threatening conditions, or death. The primary exposure and outcome were CYP2D6 genotype and metoprolol-associated ADRs respectively. We obtained Allele frequencies from gnomAD for European (EUR), East Asian (EAS), and African (AFR) populations. Descriptive statistics was used to summarize ADR frequencies and demographics whereas Chi-square tests compared ADR rates by sex and ancestry Odds ratios (OR), 95% confidence intervals (CIs) and p-values quantified associations. Data processing & analysis was performed using Python. Public de-identified data exempted from ethical approval. Results: A total of 10,407 ICSRs were included; 53.6% female, 38.6% male. Over 300 ADRs were reported including drug ineffective (3.4%) & bradycardia (3%). Serious ADRs occurred in 22% of cases. CYP2D6*4 (no function) allele frequency was ~20% in EUR but rare in EAS, where *1 and *2 alleles predominate. EUR showed higher odds of bradycardia (OR 1.42, 95% CI 1.12–1.80, p=0.002) compared to other ancestries. No significant sex differences in ADR rates were observed (p=0.19). Conclusion: CYP2D6 genetic polymorphism is related to variable risk of ADRs with metoprolol in patients with hypertension, with population-dependent allele frequencies determining risk profiles. These data lend credence to the possible utility of genotype-stratified beta-blocker treatment in hypertension.