Inclusion Criteria:
* Has a histologically-confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component (with or without sarcomatoid features) (may include participants with a diagnosis of von Hippel-Lindau \[VHL\] associated ccRCC).
* Has experienced disease progression on or after having received at least one previous systemic treatment for advanced ccRCC.
* Shows adequate organ function.
* Male participants are eligible to participate if they are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of study intervention.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or is abstinent from heterosexual intercourse during the intervention period and for at least 30 days after the last dose of study intervention.
Exclusion Criteria:
* Has hypoxia, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
* Has any history of or current brain or meningeal metastasis.
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft surgery (CABG) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
* Has moderate to severe hepatic impairment.
* Has an active infection requiring therapy (includes tuberculosis).
* Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections or is known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) deoxy ribonucleic acid (DNA) or hepatitis C antibody or ribonucleic acid (RNA).
* Has a history or current evidence of a gastrointestinal (GI) condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function.
* Has had major surgery ≤3 weeks prior to first dose of study intervention.
* Has received prior treatment with belzutifan.
* Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks prior to the first dose of study intervention.
* Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with a ≤ Grade 2 neuropathy may be eligible.
* Has received prior radiotherapy within 2 weeks prior to randomization.
* Has received colony-stimulating factors (CSFs) (e.g., granulocyte-CSF \[G-CSF\], granulocyte monocyte-CSF \[GM-CSF\] or recombinant erythropoietin \[EPO\]) ≤28 days prior to the first dose of study intervention.
* Has participated and received study intervention in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks since the last dose of the previous investigational agent.
