Abstract Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the Finite Element Method (FEM). In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open. Author summary 3D imaging of cellular components and associated reconstruction methods have made great strides in the past decade, opening windows into the complex intracellular organization. These advances also mean that computational tools need to be developed to work with these images not just for purposes of visualization but also for biophysical simulations. In this work, we present our recently rewritten mesh processing software, GAMer 2, which features both mesh conditioning algorithms and tools to support simulation setup including boundary marking. Using a workflow that consists of other open-source softwares along with GAMer 2, we demonstrate the process of going from electron micrographs to simulations for several scenes of increasing length scales. In our preliminary finite element simulations of reaction-diffusion in the generated geometries, we reaffirm that the complex morphology of the cell can impact processes such as signaling. Technologies such as these presented here are set to enable a new frontier in biophysical simulations in realistic geometries.