• Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic RCC with clear cell component (with or without sarcomatoid features).

• Has received no other prior systemic therapy for treatment of advanced/metastatic ccRCC except for adjuvant (PD-(L)1) therapy.

• Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy.

• Has measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR.

• Is able to swallow oral medication.

• Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.

• Participants receiving bone resorptive therapy (must have therapy initiated at least 2 weeks before allocation/randomization).

• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤140/90 mm Hg with no change in antihypertensive medications within 1 week before allocation/randomization.

• Has adequate organ function.

• A participant assigned male sex at birth, capable of producing sperm, continues contraception at least 7 days after the last dose of Belzutifan, and at least 96 days after the last dose of Zanzalintinib. Refrains from donating sperm and abstains from penile-vaginal intercourse and remains abstinent, or uses external condom or contraceptives consistent with local regulations.

• A participant assigned female sex at birth is not breast feeding at least 96 days after the last dose of study intervention. A participant of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test before the first dose of study intervention. A POCBP uses a highly effective contraceptive method, and continues using contraception at least 30 days after the last dose of Belzutifan, and at least 186 days after the last dose of Zanzalintinib.