Chimeric Antigen Receptor (CAR) T-cell therapies have revolutionized the treatment of hematologic malignancies. Nevertheless, challenges such as T-cell exhaustion, patient variability, antigen loss, and complex manufacturing processes limit their efficacy in autologous settings. This thesis presents novel precision immune cell engineering strategies to enhance CAR T-cell persistence and address autologous dysfunction. By targeting and disrupting the methylcytosine dioxygenase 2, TET2, we prevent terminal exhaustion and promote maintenance of memory-like populations. Our work culminated in the development of TET2-disrupted CAR T-cell with a CAR knock-in at the TRAC locus, facilitating allogeneic potential, demonstrating enhanced proliferation and tumor control in leukemia models. Building on these findings, this thesis also investigates alternative approaches to allogeneic CAR T-cell therapies for vulnerable patient populations where autologous CAR manufacturing and editing is not always feasible, such as the setting of HIV-associated malignancies. Here, we engineer γ9δ2 T-cells by integrating a CAR targeting CD19 into the CCR5 locus, thereby disrupting CCR5, generating dual-functional cells that resist HIV-mediated depletion while retaining anti-tumor activity against CD19+ lymphoma and leukemia. This research employs advanced gene editing technologies and alternative cell sources to enhance the scalability of CAR T-cell therapies, overcoming inherent challenges of autologous CAR T-cell dysfunction and advancing towards improved therapeutic success.