The paper-drying process is very energy inefficient. It almost consumes one-third of the total energy used in papermaking. This work is intended to numerically illustrate the impact of an ultrasound (US) mechanism on paper drying during a two-tiered, multi-cylinder dryer section of a paper machine, under a given set of operating conditions. Piezoelectric transducers generate ultrasound, and liquid water mist is ejected from the porous media. The drying rate of hand-sheet paper in the presence of direct-contact ultrasound is measured experimentally. The experimental results are used to generate a preliminary drying rate correlation as a function of average dry-basis moisture content. The drying section of a paper machine is simulated by a theoretical drying model, which includes a paper shrinkage model. In the model, the ultrasound modules are “retrofitted” in the dryer pockets. These alter the boundary conditions by utilizing the obtained preliminary empirical correlation. Temperature and moisture profiles are estimated for cases with and without the US. The results show that the estimated liquid flux of ultrasound misting is minimal compared to the vapor flux of surface evaporation. In addition, the US is only applied to 12% of the total dryer wrap, corresponding to half the distance between dryers. Subsequently, the US improves the drying performance by approximately 5%, although the effect of US in a direct-contact set-up is an overprediction, compared to the more practical air-borne US set-up for a papermaking machine. It is concluded that the application of ultrasound is not favorable on the multi-cylinder dryer section with low moisture content levels for the studied conditions. This work does not imply that the US mechanism is not applicable for enhancing the efficiency of paper drying process. Future study will examine the effect of US on higher moisture content levels on the paper machine, such as before or immediately after the pressing section and the paper coating section.