The use of iodine-based contrast agent for better delineation of tumors in breast CT (bCT) has been shown to be compelling, similar to the tumor enhancement in contrast-enhanced breast MRI. Contrast-enhanced bCT (CE-bCT) is a relatively new tool, and a structured evaluation of different imaging parameters at play has yet to be conducted. In this investigation, data sets of acquired bCT images from 253 patients imaged at our institution were used in concert with simulated mathematically inserted spherical contrast-enhanced lesions to study the role of contrast enhancement on detectability. To quantitatively evaluate the improvement in lesion detectability due to contrast enhancement across lesion diameter, section thickness, view plane, and breast density using a pre-whitened matched filter (PWMF) model observer. The relationship between iodine concentration and Hounsfield units (HU) was measured using spectral modeling. The lesion enhancement from clinical CE-bCT images in 22 patients was evaluated, and the average contrast enhancement (ΔHU) was determined. Mathematically generated spherical mass lesions of varying diameters (1, 3, 5, 9, 11, 15mm) and contrast enhancement levels (0, 0.25, 0.50, 0.75, 1) were inserted at random locations in 253 actual patient bCT datasets. Images with varying thicknesses (0.4-19.8mm) were generated by slice averaging, and the role of view plane (coronal and axial planes) was studied. A PWMF was used to generate receiver operating characteristic (ROC) curves across parameters of lesion diameter, contrast enhancement, section thickness, view plane, and breast density. The area under the ROC curve (AUC) was used as the primary performance metric, generated from over 90,000 simulated lesions. An average 20% improvement (ΔAUC=0.1) in lesion detectability due to contrast enhancement was observed across lesion diameter, section thickness, breast density, and view plane. A larger improvement was observed when stratifying patients based on breast density. For patients with VGF≤40%, detection performance improved up to 20% (until AUC →1), and for patients with denser breasts (VGF>40%), detection performance improved more drastically, ranging from 20% to 80% for 1- and 5-mm lesions. For the 1mm lesion, detection performance raised slightly at the 1.2mm section thickness before falling off as thickness increased. For larger lesions, detection performance was generally unaffected as section thickness increased up until it reached 5.8mm, where performance began to decline. Detection performance was higher in the axial plane compared to the coronal plane for smaller lesions and thicker sections. For emerging diagnostic tools like CE-bCT, it is important to optimize imaging protocols for lesion detection. In this study, we found that intravenous contrast can be used to detect small lesions in dense breasts. Optimal section thickness for detectability has dependencies on breast density and lesion size, therefore, display thickness should be adjusted in real-time using display software. These findings may be useful for the development of CE-bCT as well as other x-ray-based breast imaging modalities.