SimuCell3D is a three-dimensional simulation tool that enables the detailed modeling of tissue mechanics with subcellular resolution. It simulates large tissues with features such as cell polarization, growth, proliferation, extracellular matrix, fluid cavities, nuclei, and non-uniform mechanical properties. The software allows for the import of tissue geometries from microscopy images and can simulate biomechanical parameters to infer tissue behavior. SimuCell3D is efficient and open-source, enabling large-scale in silico studies of tissue organization in development and disease. The tool accounts for cell polarity by allowing different mechanical parameters on cell surfaces, enabling the simulation of tissue structures such as pseudostratified epithelia. SimuCell3D can simulate various tissue geometries, including spheroids, vesicles, sheets, and tubes, and can model intra- and extracellular entities like nuclei, lumens, and ECM. It also allows for the simulation of cell division and death, with cell division occurring rapidly and efficiently. SimuCell3D uses a biophysical model that accounts for the mechanical properties of cells and their interactions. It incorporates a detailed energy potential that includes terms for internal pressure, membrane area regulation, and surface tension. The software also includes two contact models for simulating intercellular interactions, one based on elastic forces and the other based on direct force transfer between cells. The tool has been validated through simulations of tissue growth and morphogenesis, demonstrating its computational efficiency and stability. SimuCell3D can simulate exponential growth of tissues with high cell division rates, and it has been shown to be more efficient than other 3D cell-based models in terms of computational performance. SimuCell3D has been used to study the impact of biomechanical cell properties on tissue structure, including the transition from monolayer to multilayer tissue and the formation and maintenance of pseudostratification in epithelia. The simulations have shown that tissue layering is primarily governed by cortical tension, and that cell surface tension and adhesion strength play key roles in determining tissue morphology. The software also allows for the simulation of nuclear mechanics and the effects of nuclear surface tension on cell deformation. SimuCell3D can be extended to include additional features such as subcellular components, frictional forces, and reaction-diffusion models, enabling the study of complex biological processes at high resolution. The tool is open-source and freely available, with source code and data publicly accessible.SimuCell3D is a three-dimensional simulation tool that enables the detailed modeling of tissue mechanics with subcellular resolution. It simulates large tissues with features such as cell polarization, growth, proliferation, extracellular matrix, fluid cavities, nuclei, and non-uniform mechanical properties. The software allows for the import of tissue geometries from microscopy images and can simulate biomechanical parameters to infer tissue behavior. SimuCell3D is efficient and open-source, enabling large-scale in silico studies of tissue organization in development and disease. The tool accounts for cell polarity by allowing different mechanical parameters on cell surfaces, enabling the simulation of tissue structures such as pseudostratified epithelia. SimuCell3D can simulate various tissue geometries, including spheroids, vesicles, sheets, and tubes, and can model intra- and extracellular entities like nuclei, lumens, and ECM. It also allows for the simulation of cell division and death, with cell division occurring rapidly and efficiently. SimuCell3D uses a biophysical model that accounts for the mechanical properties of cells and their interactions. It incorporates a detailed energy potential that includes terms for internal pressure, membrane area regulation, and surface tension. The software also includes two contact models for simulating intercellular interactions, one based on elastic forces and the other based on direct force transfer between cells. The tool has been validated through simulations of tissue growth and morphogenesis, demonstrating its computational efficiency and stability. SimuCell3D can simulate exponential growth of tissues with high cell division rates, and it has been shown to be more efficient than other 3D cell-based models in terms of computational performance. SimuCell3D has been used to study the impact of biomechanical cell properties on tissue structure, including the transition from monolayer to multilayer tissue and the formation and maintenance of pseudostratification in epithelia. The simulations have shown that tissue layering is primarily governed by cortical tension, and that cell surface tension and adhesion strength play key roles in determining tissue morphology. The software also allows for the simulation of nuclear mechanics and the effects of nuclear surface tension on cell deformation. SimuCell3D can be extended to include additional features such as subcellular components, frictional forces, and reaction-diffusion models, enabling the study of complex biological processes at high resolution. The tool is open-source and freely available, with source code and data publicly accessible.