Abstract: Isocitrate dehydrogenase (IDH) wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recurrence rate. The recurrence process is driven by multiple complex and interwoven factors. Although the current standard treatment regimens can temporarily alleviate patients' symptoms, they still face significant challenges in effectively preventing tumor recurrence. The recurrence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability, maintenance of stem cell characteristics and mesenchymal transformation, as well as dynamic changes in the tumor microenvironment. This article aims to comprehensively summarize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms, hoping to open up new perspectives and approaches for the treatment of recurrent tumors.