Late-stage diagnosis remains a critical challenge in cancer management, as more than half of patients are identified at advanced stages of the disease. Although liquid biopsy has enabled non-invasive tracking of tumor biomarkers, the minuscule concentration of these biomarkers and the less than 0.1% frequency of mutant alleles in the early stages necessitate the deployment of tools with ultra-high sensitivity. In this regard, CRISPR-based diagnostic systems have emerged as powerful tool platforms in cancer detection due to features such as high specificity, scalability, and compatibility for integration with new technologies. This review article explores the evolution and development of key CRISPR-based platforms, including foundational systems, multiplexing strategies, ultra-sensitive assays for rare mutations, and nanometer-scale sensors. Furthermore, the efficiency and operational capabilities of these systems in identifying various types of cancer are evaluated. Finally, future perspectives are outlined toward low-cost, rapid home-testing kits, theranostic “detect and treat” systems platforms and the integration of this technology with artificial intelligence — innovations that could shift cancer management toward early and treatable detection.