Extracellular vesicles (EVs) are emerging as pivotal tools in cancer therapy, particularly in enhancing the efficacy of immunotherapies. A notable study investigated the use of afamitresgene autoleucel, an autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), in patients with relapsed/refractory metastatic solid tumors. This multicenter, dose-escalation trial demonstrated promising results, indicating that affinity-optimized T cell receptors can significantly enhance the potency of adoptive T cell therapy (ref: Hong doi.org/10.1038/s41591-022-02128-z/). In another innovative approach, engineered extracellular vesicles were utilized to deliver GSDMD-N mRNA, which induced pyroptosis, a form of inflammatory cell death that enhances systemic immune responses against tumors. This study highlighted the challenges of therapeutically delivering GSDMD to tumor cells and presented a novel EV-based delivery system that effectively addressed these challenges (ref: Xing doi.org/10.1002/smll.202204031/). Furthermore, the in situ reprogramming of tumor-associated macrophages (TAMs) using exosomes engineered with CRISPR interference and TAM-specific peptides was explored, showcasing a strategy to enhance immunotherapy efficacy by targeting the tumor microenvironment (ref: Zhang doi.org/10.1002/anie.202217089/). Collectively, these studies underscore the versatility of EVs in cancer therapy, from direct tumor targeting to modulating the immune landscape.