Background: Next-generation sequencing (NGS) of cancer specimens is a valuable diagnostic tool that can provide detailed information regarding specific somatic genetic alterations within a tumor with potential for targeted treatment. Despite the increasing availability of NGS, preliminary data by John et al. from ASCO 2021 suggested that clinical decision making is not frequently impacted by NGS results in the setting of glioblastoma. Herein, we report how NGS data impacts other primary tumor types, including astrocytoma, oligodendroglioma, and various rare subtypes. Methods: A retrospective chart review was performed to assess the proportion of brain cancer patients receiving targeted treatment instead of standard therapeutics after NGS sequencing. Pertinent medical information was ascertained from Epic and the Electronic Data Warehouse. Targeted treatments were defined as those recommended by the Tempus report for NGS-identified potentially actionable mutations. Patients were stratified into one of three categories: astrocytoma, oligodendroglioma, or other rare subtypes (including meningioma, ependymoma, ganglioma, pleomorphic xanthoastrocytoma, atypical teratoid rhabdoid tumors, glioneuronal tumors, and CNS lymphomas). Results: Of 44 Astrocytoma patients with potentially actionable mutations, four (9.1%) were treated with targeted therapy in the form of Enasidenib, ONC201, Nivolumab, and Depatuxizumab, while 40 received NGS agnostic treatment. In 37 Oligodendroglioma patients, three (8.1%) were treated with either targeted Vorasidenib or Ivosidenib, while 34 were started on NGS agnostic therapies. Lastly, four (10.0%) of 40 patients with other rare primary tumor types received either Ibrutinib, Dabrafenib+Trametinib, Vigabatrin, or Vemurafenib as targeted therapy. Avastin and/or standard Temozolomide chemotherapy were the most common NGS agnostic therapies employed by clinicians across all three subclasses. Conclusions: Although a substantial number of potentially actionable mutations were detected by NGS, the presence of this data paired with Tempus targeted recommendations rarely impacted clinician decision-making, ranging from 8.1-10.0% of the time. Despite the availability of resources to prescribe targeted treatment, providers consistently chose NGS agnostic therapies instead. Utilization of targeted treatment may become more frequent over time, as more novel agents come to market and their efficacy is further elucidated.