The profound qualitative changes of indoor air and the progressive increase in the absolute number of pollutants, combined with the scientific awareness of the health impacts deriving from spending more than 90% of one’s time inside confined spaces, have increased the attention onto the needs of well-being, hygiene, and the health of users. This scientific attention has produced studies and analyses useful for evidence-based insights into building performance. Among the main pollutants in the indoor environment, Volatile Organic Compounds (VOCs) play a central role, and the use of box-models using the mass balance approach and Computational Fluid Dynamics (CFD) models are now consolidated to study their concentrations in an indoor environment. This paper presents the use of both types of modelling for the prediction of the VOC concentration in the indoor environment and the proposal of a guide value for the Indoor Air Quality (IAQ)-oriented building design, specifically related to the indoor VOC concentration due to building materials. Methodologically, the topic is addressed through environmental sampling, the definition of the parameters necessary for the numerical models, the simulations with the box-model and the CFD, and the comparison between the results. They show a good correspondence between the modelling tools used, highlighting the central role of ventilation and allowing a discussion of the relationship between regulatory limits of emissivity of materials and Indoor Air Guide Values for the concentration of pollutants.