The review discusses the advancements in gene therapy, focusing on the delivery systems used to deliver gene therapeutic components to clinical targets. It highlights the revolution brought by CRISPR/Cas9 technology, which has enabled precise genome editing with high accuracy and efficiency. The review covers both viral and non-viral delivery systems, detailing their advantages, limitations, and recent clinical applications. Viral vectors, such as gamma retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs), are discussed for their high transduction efficiency but also their potential risks, including immune responses and cargo limitations. Non-viral delivery systems, including physical methods (microinjection, ultrasound, and electroporation) and non-viral carriers (lipid nanoparticles, extracellular vesicles, and polyplexes), are explored for their safety, versatility, and potential for in vivo delivery. The review emphasizes the importance of improving delivery methods to enhance biocompatibility and tissue targeting, ultimately reducing manufacturing costs and increasing patient access to gene therapies.The review discusses the advancements in gene therapy, focusing on the delivery systems used to deliver gene therapeutic components to clinical targets. It highlights the revolution brought by CRISPR/Cas9 technology, which has enabled precise genome editing with high accuracy and efficiency. The review covers both viral and non-viral delivery systems, detailing their advantages, limitations, and recent clinical applications. Viral vectors, such as gamma retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs), are discussed for their high transduction efficiency but also their potential risks, including immune responses and cargo limitations. Non-viral delivery systems, including physical methods (microinjection, ultrasound, and electroporation) and non-viral carriers (lipid nanoparticles, extracellular vesicles, and polyplexes), are explored for their safety, versatility, and potential for in vivo delivery. The review emphasizes the importance of improving delivery methods to enhance biocompatibility and tissue targeting, ultimately reducing manufacturing costs and increasing patient access to gene therapies.