Purpose: This study aims to identify determinants of pericardial effusion (PCE) in patients with renal cancer and predictors of in-hospital mortality in patients with renal cancer and PCE. Materials and Methods: We conducted a retrospective cohort study using National Inpatient Sample of patients with primary malignant renal cancer data from 2016–2020. A total of 85,288 patients were included in the analysis, of which 763 (0.90%) presented with PCE. The main outcomes of interest were the presence of PCE and the in-hospital mortality rate in patients with renal cancer and PCE. Results: The majority of our cohort are aged ≥40 years (96.79%) and males (64.57%). In the bivariate analysis, patients <40 years had higher odds of PCE (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.23–2.63). Non-Hispanic Black (aOR, 1.59; 95% CI ,1.30–1.94) and Hispanic patients were associated with an increased odd of PCE odds ratio. Higher Elixhauser comorbidity index (≥4: aOR, 2.27; 95% CI, 1.66–3.08), hypoproteinemia (aOR, 1.49; 95% CI, 1.22–1.81), heart failure (aOR, 2.15; 95% CI 1.83–2.55), metastatic disease (aOR, 1.36; 95% CI, 1.15–1.62), and severe disease presentation (aOR, 6.35; 95% CI, 4.82–8.36) were also significant predictors of PCE. Private insurance was associated with higher PCE odds (aOR, 1.43; 95% CI, 1.20–1.70). Among PCE patients, the in-hospital mortality rate was 13.37%. Self-pay insurance status (aOR, 3.82; 95% CI, 1.05–13.95), metastatic disease (aOR, 1.76; 95% CI, 1.07–2.96), and severe disease presentation (aOR, 3.46; 95% CI, 1.05–8.58) significantly predicted increased mortality. Conclusion This study identifies crucial demographic, clinical, and healthcare system factors associated with PCE and in-hospital mortality in renal cancer patients. These findings highlight the need for increased vigilance and tailored surveillance for vulnerable groups and those with higher comorbidity burdens.