Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, we systematically summarized the synergistic mechanisms between NPs and CAR-T cell therapy, including optimization of genetic modification, enhancement of tumor site infiltration, modulation of immunosuppressive tumor microenvironments, mitigation of tumor antigen heterogeneity, real-time monitoring, and dynamic control of cellular activity. Ultimately, it highlights the emerging paradigm of artificial intelligence integration within this domain while discussing the associated technical obstacles and future prospects of this combined therapeutic approach.