Genomic instability is a critical factor in glioma progression and treatment resistance. This study investigates the correlation between genomic instability metrics and glioma grades, treatment response, and overall survival. We analyzed 400 glioma cases, assessing mutation frequency, chromosomal instability scores, and copy number variations (CNVs). Our findings reveal that higher glioma grades are associated with increased genomic instability, including elevated mutation frequency and chromosomal instability. Patients with resistant gliomas showed significantly higher genomic instability metrics compared to those with partial or full treatment sensitivity. Furthermore, Kaplan Meier survival curves demonstrated that high genomic instability correlates with poorer overall survival. These results underscore the role of genomic instability as a critical factor in glioma aggressiveness and therapeutic resistance. Incorporating genomic instability metrics into clinical practice could enhance diagnostic accuracy and inform more effective treatment strategies, potentially improving patient outcomes. Our research highlights the need for ongoing investigation into genomic instability as a prognostic and predictive tool in glioma management.