Adoptive cell therapy (ACT) is a ground-breaking development in cancer treatment that uses modified immune cells to target and eradicate tumors precisely. ACT is a type of immunotherapy in which T cells are genetically manipulated to produce chimeric antigen receptor (CAR) T cells, tumor-infiltrating lymphocytes (TILs), and T cell receptors. CAR-T cell therapy, with its promising effects, has transformed the area of ACTs, notably for hematologic malignancies. ACT is not ideal, and it can cause significant side effects, limiting its use in clinical trials. One of the most promising approaches to reducing side effects is to give adoptive T cells the ability to target neoantigens, which are unique to tumor cells. In this review, we focused on the principles, benefits, challenges, and pre-clinical, translational, and clinical research on ACT, as well as safety concerns such as cytokine release syndrome and neurotoxicity. We also discussed combination approaches, personalized approaches, and emerging technologies involved in maximizing ACT efficacy.