CRISPR-Cas genome editing is a promising tool for treating genetic diseases, but its clinical translation requires efficient and safe delivery methods. This review discusses recent advances in nonviral delivery of CRISPR-Cas genome editors, including ribonucleoproteins (RNP) and mRNA, which offer advantages over viral vectors such as transient expression and reduced immunogenicity. These methods are already being used in clinical trials for diseases like sickle cell disease and beta-thalassemia. However, targeted delivery to specific cell types or organs remains a challenge. Ex vivo delivery methods, such as isolating hematopoietic cells and using electroporation, have shown success in editing T cells and hematopoietic stem cells. In vivo delivery methods, including direct injection and nanoparticle-based delivery, are also being explored to target tissues like the liver, brain, and tumors. Nanoparticles, such as lipid nanoparticles (LNPs) and synthetic nanoparticles, are being developed to improve targeting and reduce off-target effects. Additionally, enveloped delivery vehicles (EDVs), including virus-like particles and extracellular vesicles, are being investigated for their ability to deliver genome editors to specific cells. While ex vivo methods have shown promise, in vivo delivery remains a major challenge due to the need for cell-type specificity and the risk of off-target effects. Future research aims to develop more efficient and targeted delivery systems to enable broader clinical applications of CRISPR-Cas genome editing.CRISPR-Cas genome editing is a promising tool for treating genetic diseases, but its clinical translation requires efficient and safe delivery methods. This review discusses recent advances in nonviral delivery of CRISPR-Cas genome editors, including ribonucleoproteins (RNP) and mRNA, which offer advantages over viral vectors such as transient expression and reduced immunogenicity. These methods are already being used in clinical trials for diseases like sickle cell disease and beta-thalassemia. However, targeted delivery to specific cell types or organs remains a challenge. Ex vivo delivery methods, such as isolating hematopoietic cells and using electroporation, have shown success in editing T cells and hematopoietic stem cells. In vivo delivery methods, including direct injection and nanoparticle-based delivery, are also being explored to target tissues like the liver, brain, and tumors. Nanoparticles, such as lipid nanoparticles (LNPs) and synthetic nanoparticles, are being developed to improve targeting and reduce off-target effects. Additionally, enveloped delivery vehicles (EDVs), including virus-like particles and extracellular vesicles, are being investigated for their ability to deliver genome editors to specific cells. While ex vivo methods have shown promise, in vivo delivery remains a major challenge due to the need for cell-type specificity and the risk of off-target effects. Future research aims to develop more efficient and targeted delivery systems to enable broader clinical applications of CRISPR-Cas genome editing.