The coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has changed the landscape of healthcare globally. Particularly challenging clinical scenarios arise in the care of cancer patients who have high-risk disease and are at greater risk of developing a severe, life-threatening COVID-19 if exposed to SARS-CoV-2. The mortality rate is significantly higher among SARS-CoV-2 infected patients with active cancer than those with other co-morbidities. The molecular mechanism of SARS-CoV-2 infection is intimately intertwined with the kidney. Structural spike (S) proteins drive entry of the virus into target host cells by engaging the cellular receptor ACE2. ACE2 facilitates the attachment of the virus to target cells. As ACE2 is expressed on podocytes and the border of the proximal tubule cells of the kidney, among other organs, there is an easy route of infection for the viral particles at this site (Figure 1). This review from Mount Sinai Health in New York City, the pandemic epicenter, sought to analyze the COVID-19 impact on the kidney and renal cell carcinoma, as well as potential therapeutic targeting for renal cell carcinoma (RCC) patients with COVID-19.