BACKGROUND: Recently, cancer treatment paradigms have shifted dramatically with the advent of immunotherapies, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite it is revolutionary positive outcomes in treating hematologic malignancies, challenges such as severe toxicities, high treatment costs, and limited efficacy in solid tumors persist. This review highlights these limitations and the ongoing need for innovation in CAR T-cell therapy. MAIN BODY: This manuscript provides a comprehensive review of most current advancements in CAR T-cell therapy, with a focus on targeting its immunotherapeutic principles, modification of T cells for Targeted cancer therapy using T cells, and clinical applications. It explores the key elements of CAR T-cell therapy, containing antigen recognition domain and intracellular signaling domains, which enable T cells to interact with cancer cells and exert cytotoxic effects. The review examines approved therapies, and ongoing clinical trials, Along with obstacles like cytokine release syndrome (CRS), neurotoxicity, along antigen escape mechanisms. Furthermore, innovations in cutting-edge CAR T-cell therapies and personalized treatment approaches are discussed, together with an emphasis on improving safety and efficacy. CONCLUSION: The manuscript outlines the future outlook on integrating CAR T-cell therapy integrated with other treatments and exploring patient-specific approaches to revolutionize cancer care. This review aims to bridge the existing gaps in research, offering valuable insights for students and researchers in biomedical sciences and oncology.