Dragos Cretoiu 1, 2 *
1 Discipline of Medical Genetics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 2 Polizu Clinical Hospital, Alessandrescu Rusescu National Institute of Mother and Child Health, Bucharest, Romania
*Correspondence to: Dragos Cretoiu, Polizu Clinical Hospital, Alessandrescu Rusescu National Institute of Mother and Child Health, Bucharest, Romania. E-mail: dragos@cretoiu.ro
Abstract
Personalized pharmacotherapy harnesses patient-specific information—especially genetic data—to tailor drug se-lection and dosing for optimal safety and efficacy. Next-generation sequencing (NGS) technologies have revolu-tionized the ability to interrogate the genome, uncovering both common polymorphisms and rare variants that influence drug response. This narrative review discusses the theoretical foundations of pharmacogenomics as en-abled by NGS, highlights emerging sequencing technologies and bioinformatic tools that are advancing the field, and examines the clinical utility of NGS-driven pharmacotherapy across diverse medical domains. We summarize how comprehensive genomic profiling can inform drug metabolism and efficacy predictions, describe cutting-edge approaches (such as long-read sequencing and machine learning) that address current challenges, and review re-cent evidence supporting the implementation of multi-gene pharmacogenomic testing in clinical practice. While NGS-powered pharmacogenomics holds great promise to improve medication outcomes and reduce adverse drug reactions, we also consider the practical hurdles—technical, interpretive, and regulatory—that must be overcome for its broad integration into routine care. Implementing NGS for personalized pharmacotherapy decisions requires a confluence of robust genomic technologies, advanced informatics, and carefully crafted clinical workflows. With continued innovation and evidence generation, NGS-guided pharmacotherapy is poised to become a cornerstone of precision medicine, enabling truly individualized drug therapy.