The objective of our study is to optimize the acquisition parameters for imaging Ag2S nanoparticles using contrast-enhanced digital mammography (CE-DM) by varying parameters such as kV, mAs, and filtration. The efficacies of three different contrast materials (Ag2S nanoparticles, silver nanoparticles, and iodine) were assessed using a contrast-embedded gradient phantom. The phantom was constructed using tissue-equivalent materials and varied continuously in composition from 100% glandular tissue to 100% adipose tissue. Each contrast agent was prepared at six different concentrations (1, 2, 5, 10, 15, and 25 mg/mL). Holes were bored through the phantom in the direction of varying glandularity, and tubes of contrast agents were inserted into the holes. Phantoms were imaged at four different energies (26 kV, 32 kV, 45 kV, and 49 kV); 5 energy pairs were considered in this study. Our results demonstrate that for a given contrast agent, the contrast-to-noise ratio is linearly proportional to concentration, and its magnitude is dependent on the energy of the low-energy (LE) image. In our study, it was shown that the LE images at 26 kV are better suited for imaging silver-based nanoparticles, and the LE images at 32 kV are better suited for imaging iodine contrast. Thus, the energy of the LE image should be chosen so that it is as close as possible to the k-edge of the contrast material. Preliminary results from CE-DM imaging indicate that silver contrast has a significantly higher signal than iodine contrast when imaging at lower energies, thus demonstrating the feasibility of using silver-based nanoparticles in breast imaging.