In this chapter, we have narrated the impact of advanced CRISPR/Cas-9 technology with a blend of other genomic tools on RNA-based therapeutics. Since the discovery of RNA interference, the potential of this technique in genomic target-specific therapeutics has been acknowledged. In the last decade, with the discovery of CISPR/Cas-9 technique the hope for genome editing-based therapies has seen a hike. This chapter begins by providing an overview of CRISPR/Cas-9 advancements and historical development in establishing this tool as a potent therapeutic intervention. It further provides an outline of different delivery systems for improved targeting specificity and reduced off-target effects. A brief comparison of different types of RNA-based therapies such as antisense oligonucleotides, small interfering RNAs (siRNAs), aptamers, and messenger RNAs has been made followed by a perspective on its amalgamation with CRISPR/Cas-9 for target-specific gene editing. Furthermore, this chapter addresses challenges and future directions with a focus on ethical considerations and the future potential of CRISPR/Cas-9-based personalized genomic medicine.