Chimeric antigen receptor (CAR) cell therapy demonstrates a groundbreaking shift in combating cancer, showing significant advancements in both hematological and non-hematological malignancies. This book chapter explores the dynamic landscape of CAR-T and CAR-natural killer (NK) cells as potent immunotherapeutic modalities. It delves into the intricate mechanisms underlying their efficacy, highlighting their ability to recognize and eradicate cancer cells while sparing healthy tissues precisely. Crucial considerations such as target antigen selection, optimization of CAR design, and strategies to enhance immune cell persistence are discussed. We aimed to navigate through the latest developments in harnessing CAR-NK and CAR-T cells for the treatment of various malignancies, including leukemias and lymphomas, as well as solid tumors. Furthermore, besides their limitations, this chapter elucidates the distinct attributes of CAR-T and CAR-NK cells in preclinical and clinical studies.