Abstract: Universal CAR-T (UCAR-T) therapy utilizes immune cells from healthy donors to enable mass production of off-the-shelf CAR-T cell products, addressing issues of high cost and long preparation times associated with conventional autologous CAR-T cells. Products specific to various targets have already entered clinical assessment, and the application of gene-editing technologies has reduced the risk of graft-versus-host disease (GvHD). In recent years, alternative universal cell sources (including NK cells, NKT cells, and γδT cells) have attracted much attention due to their natural avoidance of GvHD, providing greater product safety guarantees. Moreover, personalized designs based on characteristics of different cell types have also opened new possibilities for improving therapeutic efficacy. This review summarizes the main advances in clinical research, latest technical strategies, and core challenges faced by allogeneic CAR-based cell therapy, aiming to provide a reference for researchers and physicians seeking a better balance between efficacy and safety, and further expanding its clinical application.