Since virtually no trials have evaluated the effectiveness of temozolomide (TMZ) in the treatment of spinal cord (SC) glioblastoma multiforme (GBM), we conducted a systematic review to evaluate its efficacy. Primary SC GBM is rare. Its management remains unclear, even though treatment guidelines have been established since 2005 for its cranial counterpart. We performed a medical subject heading search with the terms “glioblastoma” and “primary spinal cord neoplasms, intramedullary”. We stratified the papers into two groups according to the use of TMZ, and analyzed survival rates using the Kaplan–Meier method with a two-sided log-rank scale. The TMZ subgroup contained nine articles and a total of 19 patients with primary SC GBM who were treated with adjuvant TMZ. The non-TMZ group consisted of 19 articles including 45 patients who underwent other treatment modalities. The TMZ subgroup had an overall survival of 16 months, compared to the non-TMZ group with a median overall survival of 10 months. The difference between these two groups was not statistically significant (p = 0.57). While this review did not demonstrate a statistically significant difference in long term survival between patients with SC GBM treated with TMZ versus those not treated with TMZ, a slightly longer survival time was seen in the TMZ group. The small number of patients is likely a contributing factor to the lack of statistical significance. Our analysis highlights the need for a multi-institutional, prospective, controlled study to evaluate the use of TMZ in the treatment of SC GBM.