This review discusses viral and non-viral systems for delivering gene therapeutics to clinical targets. CRISPR/Cas9 technology has enabled precise genome editing, which is crucial for treating genetic disorders. However, delivering the necessary components to target cells remains a challenge. Electroporation is a common method, but it can be toxic. Newer, less disruptive methods now allow safe and efficient delivery of multiple components for precise genome editing, expanding the applicability of these strategies. The review highlights various delivery systems, including viral and non-viral, emphasizing their advantages, limitations, and recent clinical applications. Recent improvements in delivery methods for cell specificity are critical for future in vivo targeting and will play a key role in gene therapy. Viral vectors, such as gamma retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs), have been used in gene therapy, but they pose risks like insertional mutagenesis and high manufacturing costs. Non-viral systems, such as lipid nanoparticles (LNPs) and polyplexes, offer safer and more versatile alternatives but may have lower efficiency. The review also discusses physical methods like ultrasound and electroporation for gene delivery. Extracellular vesicles, such as exosomes, are promising for delivering therapeutic molecules. LNPs are widely used for delivering mRNA and other nucleic acids, with applications in gene therapy and vaccination. Polyplexes, made from polymers like polyethyleneimine (PEI), are effective for delivering DNA or RNA but can be toxic. The review concludes that advancements in delivery systems are essential for improving the efficiency and safety of gene therapy, enabling direct in vivo delivery and reducing manufacturing costs. The development of targeted delivery strategies is crucial for the future of gene therapy.This review discusses viral and non-viral systems for delivering gene therapeutics to clinical targets. CRISPR/Cas9 technology has enabled precise genome editing, which is crucial for treating genetic disorders. However, delivering the necessary components to target cells remains a challenge. Electroporation is a common method, but it can be toxic. Newer, less disruptive methods now allow safe and efficient delivery of multiple components for precise genome editing, expanding the applicability of these strategies. The review highlights various delivery systems, including viral and non-viral, emphasizing their advantages, limitations, and recent clinical applications. Recent improvements in delivery methods for cell specificity are critical for future in vivo targeting and will play a key role in gene therapy. Viral vectors, such as gamma retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs), have been used in gene therapy, but they pose risks like insertional mutagenesis and high manufacturing costs. Non-viral systems, such as lipid nanoparticles (LNPs) and polyplexes, offer safer and more versatile alternatives but may have lower efficiency. The review also discusses physical methods like ultrasound and electroporation for gene delivery. Extracellular vesicles, such as exosomes, are promising for delivering therapeutic molecules. LNPs are widely used for delivering mRNA and other nucleic acids, with applications in gene therapy and vaccination. Polyplexes, made from polymers like polyethyleneimine (PEI), are effective for delivering DNA or RNA but can be toxic. The review concludes that advancements in delivery systems are essential for improving the efficiency and safety of gene therapy, enabling direct in vivo delivery and reducing manufacturing costs. The development of targeted delivery strategies is crucial for the future of gene therapy.