Moreover, by targeting EGFR and PLK1 oncogenes, the Cas12a RNP brain‐targeting nanocapsule system achieved higher anti‐tumor activity both in glioma cell lines in vitro and orthotopic xenografts models in vivo, exhibiting superior synergistic inhibition without inducing off‐target editing or systemic toxicity to normal tissues. Here, EGFR is linked to central nervous system cancer.