• Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior lines of treatment in the advanced or metastatic setting, and the most recent treatment must include a PD-1 or PD-L1 CPI, cabozantinib, or lenvatinib. Examples of acceptable prior regimens include: nivolumab plus ipilimumab (cohort A), pembrolizumab plus axitinib, avelumab plus axitinib, or VEGF-targeted monotherapy followed by nivolumab monotherapy (cohort B), or cabozantinib or lenvatinib with or without everolimus, received alone sequentially before PD-1/PD-L1 inhibitors, or in combination with CPIs (cohort C)

• There must be evidence of progression on or after treatment (at any point after completing prior therapy) with a PD-1/PD-L1-containing regimen as the last treatment received within 6 months of enrollment

• Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \>= 15 mm with conventional techniques or \>= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation

• Karnofsky performance status \>= 70

• Age \>= 18 years

• Hemoglobin \>= 9 g/dl (treatment allowed)

⁃ May receive transfusion

• Absolute neutrophil count \>= 1,000/uL

• Platelets \>= 75,000/uL

• Total bilirubin =\< 1.5 mg/dL

⁃ For patients with Gilbert's disease, total bilirubin should =\< 3 mg/dL (=\< 51.3 umol/L)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be \< 5 x ULN

• Serum Creatinine =\< 1.5 x ULN (as long as patient does not require dialysis)

⁃ If creatinine is not \< 1.5 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be \>= 40 mL/kg/1.73 m\^2

• Institutional normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x ULN prior to study entry. Therapeutic anticoagulation is permitted if: on a stable dose of low molecular weight heparin (LMWH) for \> 2 weeks (14 days) at the time of enrollment or on a direct oral anticoagulant (DOAC) for \> 2 weeks at time of enrollment

• Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) before study entry. Pregnancy test must be repeated if performed \> 14 days before starting study drug

• Women must not be breastfeeding

• Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy

• Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or gamma knife, without recurrence or edema for 1 month (4 weeks)