The integration of multi-omics approaches with Electronic Health Records (EHRs) has the potential to transform personalized medicine by offering deeper insights into disease mechanisms, treatment responses, and patient outcomes. By incorporating genomics, proteomics, metabolomics, and other omics layers, multi-omics enhances diagnostic accuracy, treatment optimization, and predictive modeling in clinical care. However, this advancement also raises critical ethical concerns, particularly regarding privacy, confidentiality, autonomy, and justice. Multi-omics data serves as a distinct biological identifier, making it highly sensitive and vulnerable to misuse. The potential for re-identification also remains a major concern, as linking genomic data with phenotypic information increases the risk of privacy breaches and unauthorized disclosures. Equity in multi-omics research remains a significant challenge, as genomic studies have historically been biased toward populations of European descent, restricting the generalizability of findings to diverse groups. While federal regulations such as the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. and Ontario’s Personal Health Information Protection Act (PHIPA) establish baseline legal protections, their effectiveness depends on robust digital infrastructure, public education, and the development of privacy frameworks. Robust security measures such as encryption, blockchain, and privacy-preserving algorithms are essential to mitigate risks, yet existing governance frameworks must extend beyond security protocols to establish clear regulations on data ownership, access rights, and ethical usage. Emerging challenges, including AI-driven data analysis and the commercialization of genetic information, further underscore the need for proactive governance to prevent misuse, discrimination, and bias in healthcare and insurance industries. To ensure ethical multi-omics integration into EHRs, continuous policy updates, interdisciplinary collaboration, and patient-centered approaches are essential. Balancing innovation with ethical integrity will be crucial in advancing precision medicine while safeguarding individual rights and promoting equitable healthcare access.