The main inclusion criteria include but are not limited to the following:

Has surgically resected and histologically confirmed diagnosis of Stage II, IIIA, IIIB (N2) squamous or nonsquamous NSCLC as per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.

Has no evidence of disease at the time of providing documented consent for the main study.

Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy.

No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab.

Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.

Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART).

The main exclusion criteria include but are not limited to the following:

Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma.

HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.

Received prior neoadjuvant therapy for their current NSCLC diagnosis.

Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis.

Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.

Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.

Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.

Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.

Known additional malignancy that is progressing or has required active treatment within the past 5 years.

Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.

History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Active infection requiring systemic therapy.