Here, we describe an optimized imaging methodology with dual contrast computed tomography (CT; intravenous and intraperitoneal), T2-weighted magnetic resonance imaging (MRI), and delayed 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) positron emission tomography (PET) for characterization of a recently developed Igf2 biallelic expression/Wt1 knockout mouse model of Wilms tumor [18], which allowed for more accurate repetitive anatomic and metabolic imaging during the early development and progression of Wilms tumors and their responses to experimental targeted therapies. Here, IGF2 is linked to Wilms tumor.