• Participants must have a histologically confirmed diagnosis of locally advanced, unresectable (not amenable to curative surgery or radiation therapy) or metastatic Renal Cell Carcinoma (RCC).

• Participants must have clear cell RCC (ccRCC) or non-clear cell RCC (nccRCC) may be enrolled in Part 1. Note: Part 2 may only enroll participants with ccRCC.

• Participants may have favorable, intermediate or poor risk disease categories.

• Participants must not have received prior systemic therapy for metastatic RCC, with the following exceptions:

  i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC is allowed if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.

ii) For Part 1A participants: Prior systemic therapy in the metastatic setting is allowed if the participant has not received any therapy targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) (e.g., ipilimumab).

iii) For Part 1B participants: Prior systemic therapy in the metastatic setting is allowed if the participant has not received prior treatment with cabozantinib.

- Participants must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.