Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma

Inclusion Criteria: * Age \>= 18 years * Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma) * NOTE: Grade IV IDH-mutant astrocytoma is also allowed * Neoadjuvant patients only: Have an enhancing mass on magnetic resonance imaging (MRI) amenable to \> 90% resection of contrast-enhancing tumor (as determined by the neurosurgeon pre-operatively) and histological diagnosis of glioblastoma or astrocytoma from a prior biopsy or surgery * NOTE: Biopsy or subtotal resection must have been =\< 43 days prior to registration * Neoadjuvant patients only: Willing to undergo craniotomy and resection of their brain tumor at Mayo Clinic in Rochester, Minnesota (MN) * Adjuvant patients only: Must have undergone craniotomy and resection of their brain tumor =\< 6 weeks prior to registration * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to registration) * Platelet count \>= 100,000/mm\^3 (obtained =\< 28 days prior to registration) * Hemoglobin \>= 9.0 g/dL without transfusion or erythropoietin (EPO) dependency (=\< 7 days prior to assessment) (obtained =\< 28 days prior to registration) * Prothrombin time (PT) =\< 1.5 x upper limit of normal (ULN) unless patient is receiving anticoagulant therapy and PT or partial prothrombin time (PTT) is within therapeutic range of intended use of coagulants (obtained =\< 28 days prior to …