Abstract Background Personalized medicine is an emerging field, aiming to improve the safety and efficacy of pharmacotherapy. The field’s implementation in clinical care is steadily increasing. Pharmacogenomics are one example of personalized approaches in the clinic and direct-to-consumer (DTC) pharmacogenomic tests have become publicly available. We aimed to assess public opinion on pharmacogenomic research and testing to foster integration within Belgian health care. Methods A cross-sectional survey was created and disseminated online, focusing on the citizen perspective. Participants’ willingness to engage in pharmacogenomic research was the primary outcome. In addition, their awareness, understanding, expectations and overall acceptance towards pharmacogenomic testing was investigated. Results A total of 156 participants (54.5% aged between 18 and 30 years, 45.5% > 30 years; 73.1% females) completed the survey. Half ever experienced side effects (46.2%) and treatment failure (52.6%). Up to 45.5% (n = 71) were willing to participate in pharmacogenomics research, and the majority (78.8%) were convinced that pharmacogenomic tests could help doctors to prescribe them the right medications. Additionally, 76.3% (n = 118) supported a partial reimbursement of pharmacogenomics tests. A minority (5.1%, n = 8) of participants showed interest in DTC tests, and 15.4% (n = 24) expressed privacy concerns regarding pharmacogenomics testing. Participants preferred their healthcare professionals’ to perform the test and access their data, but refused commercial providers. Conclusion Overall, participants showed a positive attitude towards precision medicine and pharmacogenomics research. Our findings may help guiding future pharmacogenomic implementation initiatives to optimize drug use by using pharmacogenomic information integrated within health care.