Recent advances in organoid technology, particularly patient-derived organoids (PDOs), have become a cornerstone in personalized medicine and cancer drug discovery. The PDOs are generated by culturing primary cancer cells from patients in three-dimensional extracellular matrices, providing a unique platform for replicating and preserving the genotype and phenotype of individual tumours. Furthermore, they have demonstrated an ability to predict the response of these organoids to various drugs, aligning with clinical outcomes. Due to their efficiency in replicating the molecular and phenotypic characteristics of patient tumours, PDOs have taken significant attention in the development of patient-centric clinical decision-making tools. This not only could assist clinicians in developing personalized treatment strategies but also plays a vital role in shaping the design of clinical trials. Moreover, the capacity to propagate PDOs ex vivo has led to the establishment of biobanking strategies, enhancing global accessibility to these invaluable resources. This facilitates the screening of numerous compounds in their developmental stages and the design of novel drug combinations involving approved drugs. With PDO studies demonstrating substantial progress in high-throughput drug screening, the drug discovery process is poised for acceleration. Notably, PDOs offer advantages in terms of time and logistics when compared to in vivo mouse model systems. In this chapter, I delve into the historical evolution, current applications, and future potential of PDO technology, emphasizing its role in advancing precision oncology and guiding clinical decision-making.