The article reviews the advancements in lipid nanoparticles (LNPs) as a promising delivery system for CRISPR-Cas9 genome editing. CRISPR-Cas9, a powerful gene-editing technology, has revolutionized biomedical research and healthcare by enabling precise modifications to genetic material. However, its limited transfection efficiency has hindered its widespread adoption. LNPs, particularly modified cationic lipid nanoparticles and solid lipid nanoparticles, show significant potential for efficient CRISPR-Cas9 delivery. The review covers the molecular mechanisms of CRISPR/Cas9, current strategies for delivering CRISPR/Cas9 tools, the advantages of LNPs, and approaches to improve genome targeting and tissue targeting. It also highlights recent clinical trials and future directions for overcoming limitations and adapting this technology for clinical use. The article emphasizes the role of LNPs in overcoming challenges such as hydrophobicity, negative charge, instability, immunogenicity, and off-target effects, making them a valuable tool for gene therapy and other therapeutic applications.The article reviews the advancements in lipid nanoparticles (LNPs) as a promising delivery system for CRISPR-Cas9 genome editing. CRISPR-Cas9, a powerful gene-editing technology, has revolutionized biomedical research and healthcare by enabling precise modifications to genetic material. However, its limited transfection efficiency has hindered its widespread adoption. LNPs, particularly modified cationic lipid nanoparticles and solid lipid nanoparticles, show significant potential for efficient CRISPR-Cas9 delivery. The review covers the molecular mechanisms of CRISPR/Cas9, current strategies for delivering CRISPR/Cas9 tools, the advantages of LNPs, and approaches to improve genome targeting and tissue targeting. It also highlights recent clinical trials and future directions for overcoming limitations and adapting this technology for clinical use. The article emphasizes the role of LNPs in overcoming challenges such as hydrophobicity, negative charge, instability, immunogenicity, and off-target effects, making them a valuable tool for gene therapy and other therapeutic applications.