See Study Implementation (Section 3.1) regarding study termination and procedures for unblinding participants . Eligibility will be evaluated by the study team according to the following criteria: Eligibility waivers are not permitted. Subjects must meet all of the inclusion and none of the exclusion criteria to be registered to the study. Study treatment may not begin until a subject is registered. Please refer to Section 2.2 for complete instructions regarding registration procedures. 2.1.1 Inclusion Criteria Pre-Surgery (Step 1) Inclusion: 2.1.1.1 MRI findings consistent with a suspected GBM or a histologically confirmed newly diagnosed GBM that has not been treated and would benefit from further surgical resection. As vaccine needs to be generated from the patient’s tumor, patients will need to be identified prior to definitive surgery. 2.1.1.2 Preliminary assessment by the neurosurgeons that >80% of the tumor can be resected with an expectation that >7gm of tissue would be resected 2.1.1.3 Age ≥ 18 years on day of signing informed consent. 2.1.1.4 Karnofsky performance status ≥ 70%. 2.1.1.5 Tumor must be supratentorial only. 2.1.1.6 Stereotactic biopsy will not be allowed unless there is plans for second surgery to remove ≥ 80 % of the tumor. 2.1.1.7 No prior treatment with radiation or chemotherapy for their GBM. 2.1.1.8 No prior treatment with carmustine wafers. 26 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 Post-Surgery (Step 2) Inclusion: 2.1.1.9 Pathology must be a GBM, MGMT promoter region determined to be unmethylated and IDH wild type, >80 % resection of contrast enhanced tumor on post operative MRI and > 7 grams of tumor resected are required otherwise patient is ineligible . 2.1.1.10 Treatment must be initiated > 14 days and < 6 weeks from surgery. 2.1.1.11 Craniotomy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of radiation. Radiation must start within 6 weeks of surgery. 2.1.1.12 Dexamethasone dose should be < 4 mg/day or steroid equivalent prior to starting treatment. If higher doses are needed, consult with Study Chair. 2.1.1.13 Female subjects 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 negative serum pregnancy test will be required. 2.1.1.14 Patients must have adequate organ and bone marrow function within 14 days prior to step 2 registration, as defined below: 2.1.1.15 Absolute neutrophil count (ANC) > 1.5 × 109/L; platelet count > 100 × 109/L; and hemoglobin (Hb) >9.0 g/dL within 7 days prior to step 2 registration. Note: The use of transfusion or other intervention to achieve Hb ≥ 9.0 g/dL is acceptable. 2.1.1.16 Total bilirubin < 1.5 × ULN (except in patients diagnosed with Gilbert’s disease) 2.1.1.17 AST (SGOT), ALT (SGPT), and alkaline phosphatase (ALP) < 2.5 × ULN 2.1.1.18 Serum creatinine < 1.5 × ULN 2.1.1.19 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×ULN or aPTT < 1.5×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. 2.1.1.20 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. Male patients who father a child should notify the treating physician. 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: oHas not undergone a hysterectomy or bilateral oophorectomy oHas had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months) 27 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 2.1.1.21 Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study. 2.1.1.22 Diagnosis must be made by surgical excision.