Abstract Background The impact of anti-angiogenic therapy (AAT) on patients with glioblastoma (GBM) is unclear due to a disconnect between radiographic findings and overall survivorship. MR spectroscopy (MRS) can provide clinically relevant information regarding tumor metabolism in response to AAT. This review explores the use of MRS to track metabolic changes in patients with GBM treated with AAT. Methods We conducted a systematic literature review in accordance with PRISMA guidelines to identify primary research articles that reported metabolic changes in GBMs treated with AAT. Collected variables included single or multi-voxel MRS acquisition parameters, metabolic markers, reported metabolic changes in response to AAT, and survivorship data. Results Thirty-five articles were retrieved in the initial query. After applying inclusion and exclusion criteria, 11 studies with 262 patients were included for qualitative synthesis with all studies performed using multi-voxel 1H MRS. Two studies utilized 31P MRS. Post-AAT initiation, shorter-term survivors had increased choline (cellular proliferation marker), increased lactate (a hypoxia marker), and decreased levels of the short echo time (TE) marker, myo-inositol (an osmoregulator and gliosis marker). MRS detected metabolic changes as soon as 1-day after AAT, and throughout the course of AAT, to predict survival. There was substantial heterogeneity in the timing of scans, which ranged from 1-day to 6–9 months after AAT initiation. Conclusions Multi-voxel MRS at intermediate and short TE can serve as a robust prognosticator of outcomes of patients with GBM who are treated with AAT.