In this study, experimental and comprehensive multidimensional numerical models are developed for the analysis of the thermal behavior of an anhydrite slab floor heating system (FHS). Three different modeling approaches are employed, including a one dimension (ID) Modelice method based on an object-oriented approach, a two dimension (2D) finite difference method (FDM), and a three dimension (3D) finite volume method (FVM), using the ANSYS/Fluent software. The comparison between the numerical results and the measured data is performed for the inlet and outlet water temperatures, the average slab surface temperature, the depth local temperatures, and the average total heat flux. Experiments and simulations were in agreement regarding the thermal response of the FHS in accordance to the well-known 2D FDM. A multi-objective sensitivity study is then performed, based on a design of experiments method (DoE) in order to analyze the effects of the design and physical control factors and their interactions on the average surface temperature and the thermal time constant. A full factorial design, generating 128 simulations based on our validated 2D FDM model is used to construct polynomial meta-models using the aforementioned thermal parameters. As a result, the water volume flow rate and the inner diameter are the most influential factors on the surface temperature, whilst the thermal time constant is shown to be considerably influenced by the slab thickness, density, and specific heat, as well as their interactions. The elicited results may be exploited in order to help practicing building engineers to optimize the FHS, and to enhance its energy performance. (C) 2018 Elsevier B.V. All rights reserved.