Personalized cancer therapy applies specific treatments to each patient. Using personalized tumor models with similar characteristics to the original tumors may result in more accurate predictions of drug responses in patients. Tumor organoid models have several advantages over pre-existing models, including conserving the molecular and cellular composition of the original tumor. These advantages highlight the tremendous potential of tumor organoids in personalized cancer therapy, particularly preclinical drug screening and predicting patient responses to selected treatment regimens. Here, we highlight the advantages, challenges, and translational potential of tumor organoids in personalized cancer therapy and focus on gene–drug associations, drug response prediction, and treatment selection. Finally, we discuss how microfluidic technology can contribute to immunotherapy drug screening in tumor organoids. Personalized cancer medicine is an approach to tailoring effective therapeutic strategies for each patient according to a tumor’s genomic characterization. There is an urgent demand for research in personalized tumor modeling to confirm the functional aspects of genomic drug response predictions in the preclinical setting. While different tumor models, such as tumor cell lines and patient-derived tumor xenografts, have been proposed, the drawbacks of each model have limited their applications as personalized tumor models. A tumor organoid, in which cellular and molecular heterogeneity of tumor cells is preserved, has emerged as a promising platform. Recently, numerous studies highlighted the application of tumor organoids in personalized cancer medicine in terms of gene–drug association treatment, the identification of new therapies, and prediction of patient outcome.