• Has histological or cytological confirmation of squamous or nonsquamous non-small cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal involvement \[N2\]) per AJCC eighth edition guidelines

• Has confirmation that either epidermal growth factor receptor (EGFR)-directed or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated as primary therapy

• Is able to undergo surgery based on opinion of investigator after consultation with surgeon

• Is able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy

• Applies to screening for the adjuvant period only, before randomization: Has not achieved pathological complete response (pCR) at surgery by local review of pathology.

• Applies to screening for the adjuvant period only, before randomization: Tumor tissue sample from surgical resection has been provided for determination of programmed cell death ligand 1 (PD-L1) and trophoblast cell surface antigen 2 (TROP2) status by central vendor before randomization into the adjuvant period

• Applies to screening for the adjuvant period only, before randomization: Confirmed to be disease-free based on re-baseline radiological assessment as documented by contrast enhanced chest/abdomen/pelvis computed tomography (CT) (or magnetic resonance imaging (MRI)) within 28 days before randomization

• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

• 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 at screening

• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at least 4 weeks before the start of study intervention