<p>Being extremely precise in terms of genetic material modifications, CRISPR/Cas9 technology has very rapidly become the cornerstone in the field of precision oncology. This review is focused on the great potential offered by CRISPR/Cas9 in terms of cancer treatment, emphasizing its cellular, biochemical, and molecular mechanisms of action. We provide a short historical background and description of its operational principles, followed by an in-depth analysis of how CRISPR/Cas9 reprograms oncogenic signaling networks by selectively modifying cancer-associated genes such as <i>KRAS</i>, <i>MYC</i>, <i>BRAF</i>, and <i>EGFR</i>, and restoring the function of tumor suppressors including <i>TP53</i>, <i>RB1</i>, and <i>PTEN</i>. The review further explores its ability to remodel cellular pathways involved in apoptosis, DNA repair, and cell-cycle regulation, alongside its modulation of key biochemical cascades. We analyse the technology’s application to epigenetic modifications and the regulation of non-coding RNAs as arising therapeutic targets. It also considers the deployment of CRISPR/Cas9 across various cancers, including haematological malignancies such as leukaemia and lymphoma and solid tumors such as breast, lung, and colorectal cancer, where it is being contextualized to disease-specific outcomes and limitations. To overcome delivery issues, recent advances in various viral vectors (AAV, lentivirus) and non-viral methods such as lipid nanoparticles, polymeric nanotechnologies, exosomes and magnetic nanoparticles are explained. In addition, findings from completed and ongoing clinical trials that demonstrate the clinical translation of CRISPR are presented. Lastly, important issues are considered, including immune reactions, off-target effects, and integration with precision oncology. When combined, these viewpoints provide a thorough understanding of the current state of CRISPR/Cas9 and its potential to revolutionize cancer treatment in the future.</p> Graphical abstract <p></p>