The new era of anticancer therapy, precision therapy or personalized treatment, entails tailoring the treatment plan to each patient’s unique genetic or biological characteristics. One of the most promising treatments that has demonstrated favorable outcomes in the treatment of malignancies is Chimeric Antigen Receptor T (CAR T)-cell therapy. The engineered receptors known as Chimeric Antigen Receptors, or CARs, are crucial for redirecting T-cells and eliminating the cells with a particular target antigen expression. This therapy involves in vitro engineering of the T-cells obtained from a patient’s blood, and expressing synthetic receptors that target a certain tumor-causing antigen. In the treatment of cancer, particularly hematologic cancers like leukemias and B-cell lymphomas, Chimeric Antigen Receptor (CAR) T-cell therapy has become a cutting-edge method. The use of CAR T-cell therapy in solid tumors, however, poses challenges such as immunosuppressive microenvironments, tumor heterogeneity, and antigen escape. Tumors can lose or mutate the target antigen (like CD19 in B-cell malignancies), leading to antigen escape, where CAR T cells do not recognize and kill the tumor cells. Genetic profiling enables the design of customized CAR constructs, including neoantigen-targeted and multi-antigen CARs, to enhance precision and reduce tumor escape and enhance precision. CAR T-cell therapy, although revolutionary, is associated with adverse side effects like Cytokine release syndrome. This chapter discusses the principles, obstacles, and breakthroughs in individualized CAR T-cell therapy for solid tumors and hematologic malignancies, emphasizing its potential to transform cancer treatment.