Honeycomb sandwich panels are widely used in the industry because of their outstanding stiffness to mass ratios. The dynamic response of such structures is known to be relatively complex especially in the mid-frequency domain where a strong orthotropy can be observed. Several equivalent models are available in the literature to understand and predict this behavior, all relying on an assumption that the geometry of the honeycomb core is periodic and perfectly known. The effect of imperfection inevitably introduced at the manufacturing stage are characterized in this work using X-ray measurements. A simple homogenization approach is proposed, allowing the prediction of the shearing properties of the core from statistics extracted from its geometry. These properties are used to predict the dynamic behavior of the structure using a multi-layer analytical model. Results are compared to Laser Doppler Vibrometer measurements, showing a very good agreement with the predictions based on X-ray pictures.