Radiation Therapy With Temozolomide and Pembrolizumab in Treating Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

* Histologically confirmed newly diagnosed glioblastoma; patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma and they received no prior treatment
* No prior treatment with radiation or chemotherapy for their GBM
* No prior treatment with carmustine wafers
* Patients who have undergone recent surgery:

  * Must be a minimum of 14 days from surgery
  * Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of registration
  * Magnetic resonance imaging (MRI) within 72 hours of surgery OR 4 weeks from surgery
* Karnofsky performance status \>= 70%
* Stable or decreasing dose of corticosteroids within 5 days prior to treatment
* Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Patients need not have measurable or evaluable disease
* Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L
* Platelet count \> 100 x 10\^9/L; or
* Hemoglobin (Hb) \> 9.0 g/dL within 7 days prior to enrollment; note: the use of transfusion or other intervention to achieve Hb \>= 9 g/dL is acceptable
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except in patients diagnosed with Gilbert's disease)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
* Alkaline phosphatase (ALP) =\< 2.5 x ULN
* Serum creatinine \< 1.5 x ULN
* International normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (APTT) as follows: in the absence of therapeutic intent to anticoagulate the patient: INR \< 1.5 or PT \< 1.5 x ULN or aPTT \< 1.5 x ULN; in the presence of therapeutic intent to anticoagulate the patient: INR or PT and aPTT within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks before registration
* Females of child-bearing potential (FOCBP) and males must agree to use two adequate contraception methods (give examples, e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

  * NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    * Has not undergone a hysterectomy or bilateral oophorectomy
    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
* Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

* Any prior treatment for the patients GBM
* Has a known diagnosis of immunodeficiency (human immunodeficiency virus \[HIV\] 1/2 antibodies) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids; attempts should be made to have patient on lowest possible dose of steroids
* History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
* Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
* Has evidence of or a history of interstitial lung disease, non-infectious pneumonitis or pneumonitis
* Has an active infection requiring systemic antibiotics within 7 days of registration
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator; examples include

  * Hypertension (defined as 160/95) that is not controlled on medication
  * Ongoing or active infection requiring systemic treatment
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness/social situations or substance abuse disorders that would limit compliance with study requirements
  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
* Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
* Has received a live vaccine within 30 days prior to the first dose of trial treatment
* Patients receiving any other investigational agents within 30 days prior to the first dose of trial treatment
* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 are not eligible; known hypersensitivity to any excipients of MK-3475