Goal: The thermoregulation mechanism is a complex system that executes vital processes in the human body. Various models have been proposed to simulate the thermoregulatory response of an adult human to environmental stimuli. However, these models generally rely on stylized phantoms that lack the anatomical details of voxel phantoms used in radiation dosimetry and shielding research. The goal of this work is to introduce voxel phantoms to thermoregulation research by modeling the physical energy exchange between tissue and its surroundings, discuss a specific challenge associated with voxel phantoms, propose a method to address this challenge, and demonstrate its application. Method: One of the major challenges in using voxel phantoms is the stair-step effect on the surface of the voxelized domain. This effect causes over-estimation of surface area, accurate knowledge of which is critical for modeling heat exchanging systems. A methodology to generate a voxel domain from medical imaging data and reduce error in the surface area caused by the stair-step effect is presented. The methodology, based on a structured mesh and finite-volume method, is demonstrated with tumors generated from magnetic resonance imaging (MRI) scans of mice. Results: The methodology discussed in the paper shows a decrease in surface area over-estimation from 50% to 15% for a sphere and 47% to 17% for tumor models generated directly from MRI scans. Conclusion: This work provides a direct method to generate a smoother domain from medical imaging data and reducing surface area error in a voxelized domain. The technique presented is independent of domain material, including tissue type, and can be extended to any homogeneous or inhomogeneous domain. The increase in surface area accuracy obtained by smoothing the voxel domain results in more accurate temperature estimates in heat transfer simulation.