Background/Objectives: The heterogenous nature of renal cell carcinomas (RCCs) is increasingly recognized. The purpose of this proof-of-concept pilot study was to evaluate correlations between multiparametric MRI (mpMRI)-derived and histopathological parameters in RCCs from spatially matched regions on both MRI and pathological examination to support targeted biopsy planning. Methods: In this prospective single-center pilot study, patients with solid renal tumors ≥2 cm undergoing nephrectomy were prospectively enrolled. Each patient underwent preoperative 3.0T-mpMRI including T2-weighted and pre-/post-contrast T1-weighted sequences, chemical-shift imaging, IVIM-DWI, and T1/T2*/R2 mapping. Tumor regions were defined jointly by a pathologist and radiologist, and identical regions of interest were assessed for each tumor region across all sequences to gain quantitative mpMRI-derived parameters. Histopathology provided quantitative regional fractions of viable tumor, fibrosis, hemorrhage, and cystic/necrotic components. Spearman’s rank correlations and univariable linear regression assessed associations between mpMRI and histopathological parameters on a regional level. Results: Across 49 tumor regions in eight patients (65.3% clear cell, 34.7% papillary RCCs), the mean viable tumor fraction was 80.9% (SD 17.6). The viable tumor fraction showed inverse correlations with nephrographic and delayed phase signal intensity changes (rho = −0.59/rho = −0.51), T1 values (rho = −0.56), true diffusion coefficient D (rho = −0.47), and ADC (rho = −0.45), and a positive correlation with R² times (rho = 0.55). Delayed and nephrographic phase signal intensity changes (R² = 0.41/R² = 0.39) were the strongest single exploratory imaging correlates of viable tumor fraction. Conclusions: These findings support the feasibility of quantitative mpMRI parameters to capture regional intratumoral heterogeneity in RCCs, thereby highlighting regions with high viable tumor burden, which may help to refine the imaging-based assessment of RCCs in the future.