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Colorectal cancer (CRC) is the third most common malignancy worldwide, while it is the second most prevalent cancer for both males and females in Saudi Arabia. Intrinsic or acquired resistance to chemotherapy treatments - due to high inter- and intra-patient tumor genetic variability - causes 90% fatal disease relapse in patients already progressed to the metastatic stage. Therefore, the “one serves all” treatment principle is outdated and does not reflect our current knowledge of genetically-impacted patient-to-patient heterogeneity. Given the severity of the disease and its impact on society, there is an urgent need to develop a platform that will allow for advancing molecular and drug screening protocols for patients, in an effort to reach personalized treatment and to advise the medical staff. In this project, we aim to initiate the establishment of the first organoid platform for personalized genetic and drug screening in Saudi Arabia, based on 3D scaffolds made of own-developed ultrashort self-assembling peptides. We will use them in an organ-on-a-chip (OoC) system that will allow high-throughput screening of CRC constructs derived from patients’ samples under varying conditions. This system will allow the study of the genome and transcriptome for data analysis and modeling of the dynamics of the CRC microenvironment. We will develop a genetic database for risk variants within the Saudi population, and use the OoC to model the effects of drugs in CRC organoids. Once this platform is established, we will recreate in vitro the unique genetic background and tissue complexity of individual Saudi patients. All these technologies, the biomimetic peptides, the OoC system, the in silico modeling, and the genome/transcriptome analysis, will allow the further development of personalized medicine tools focusing on CRC molecular characteristics within the Saudi population. In summary, based on our experience in tissue engineering, biomaterial design, and in silico approaches, together with a strong team of medical doctors, and colorectal cancer biologists, we will investigate the capability of our self-assembling bioactive peptides for genetic and phenotypic 3D organoid cultures and their application in reliable personalized medicine, specifically when using OoCs as screening systems.