Nucleic acid-based therapeutics have rapidly advanced from conceptual tools to frontline clinical modalities, reshaping the landscape of precision medicine. Key platforms, including antisense oligonucleotides, small interfering RNAs, messenger RNAs, aptamers, and CRISPR-based genome editors, demonstrate the versatility of nucleic acids in silencing, correcting, or reprogramming gene expression. Central to their success are delivery innovations, particularly lipid nanoparticles (LNPs) and bioconjugates, which provide stability, enable targeted uptake, and broaden tissue accessibility. Breakthroughs such as selective organ-targeting LNPs, chemical conjugation strategies like GalNAc, and machine learning-guided optimization are redefining delivery from empirical design to predictive engineering. Alongside these advances, chemical modifications enhance durability and mitigate immunogenicity, while computational and mechanistic modeling accelerate the translation of these findings into clinically viable formulations. Clinically, nucleic acid medicines now span rare genetic disorders, oncology, infectious disease vaccines, and emerging gene-editing trials, with mRNA-based COVID-19 vaccines serving as a landmark proof of concept. Looking ahead, the convergence of precision targeting, AI-driven design, and next-generation editing platforms positions nucleic acid therapeutics to evolve into one-time, potentially curative interventions across a wide spectrum of diseases.