This systematic review explores the advancements and challenges in chimeric antigen receptor (CAR) T-cell therapy, with a focus on solid tumors, hematologic malignancies, toxicity management, and innovative CAR designs. Synthesized using Synthory.AI and adhering to PRISMA guidelines, the review analyzed 199 studies published between 2000 and 2025. Key findings highlight significant progress in targeting strategies, therapeutic efficacy, and engineering innovations, while underscoring persistent challenges such as antigen heterogeneity, toxicity management, and scalability of manufacturing. The review emphasizes the need for standardized protocols, humanized models, and combinatorial approaches to optimize safety and long-term outcomes. CAR T-cell therapy holds transformative potential, but further research is required to address its limitations and broaden its applicability.