This study will evaluate the use of nivolumab before surgery in patients with high-risk clear cell renal cell carcinoma who are eligible for nephrectomy. Nivolumab is an antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1).

Inclusion Criteria (abbreviated):

1. Confirmed non-metastatic high-risk clear cell renal cell carcinoma (T2a-T4NanyM0 or TanyN1M0)
2. Schedule to undergo either partial or radical nephrectomy as part of treatment plan
3. Patient agrees to have a tumor biopsy
4. ECOG performance status of 0 or 1
5. Adequate organ and marrow function defined by study-specified laboratory tests
6. Must use acceptable form of birth control while on study and for approximately 31 weeks post-treatment completion
7. Willingness and ability to comply with scheduled visits, treatment plans, lab tests and other study procedures

Exclusion Criteria (abbreviated):

1. Other active malignancies within last 3 years (with some exceptions for skin, prostate, cervical, or breast cancer)
2. Need for urgent or emergent nephrectomy to relieve symptoms
3. Prior treatment for RCC including surgery, radiation, thermoablation or systemic therapy
4. Surgery within 28 days of starting study treatment (some exceptions for minor procedures)
5. Received live vaccine for infectious diseases within 28 days of starting study treatment
6. Prior treatment with any antibody or drug targeting T-cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc)
7. Use of immunosuppressive doses of systemic medications within 14 days prior to starting study drug.
8. Current use of immunosuppressive agents
9. History of severe hypersensitivity reaction to other monoclonal antibodies
10. Current signs or symptoms of severe progressive or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC
11. Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements.
12. Active infection requiring therapy.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
14. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
15. History of autoimmune disease or syndrome requiring systemic steroids or immunosuppressants (some exceptions apply).
16. Pulse oximetry of <92% on room air
17. Pregnant or breastfeeding women