The CRISPR-Cas9 system has emerged as a transformative technology in genetic engineering, enabling precise and efficient genome editing across a wide range of model organisms. This comprehensive review provides an in-depth examination of CRISPR-Cas9 applications in five key model systems: Mus musculus (mice), Drosophila melanogaster (fruit flies), Danio rerio (zebrafish), Caenorhabditis elegans (nematodes), and Arabidopsis thaliana (plants). We detail the molecular mechanisms of CRISPR-mediated editing, including double-strand break repair pathways and recent innovations in precision editing tools. The review systematically compares editing approaches, efficiencies, and optimization strategies across different organisms, supported by 25 case studies of successful genetic modifications. We analyze current challenges such as off-target effects, delivery limitations, and germline transmission efficiency, presenting solutions developed through protein engineering and novel delivery methods. The discussion extends to emerging CRISPR technologies including base editing, prime editing, and epigenetic modulation, with particular attention to their applications in functional genomics and disease modeling. Finally, we outline future directions in the field, including single-cell editing, in vivo delivery systems, and computational prediction tools, providing researchers with a comprehensive resource for implementing CRISPR technologies in diverse model organisms.