The control of ventilation systems is often performed by automatic algorithms which often do not consider the future evolution of the system in its control politics. Digital twins allow system forecasting for a more sophisticated control. This paper explores a novel methodology to create a Machine Learning (ML) model for the predictive control of a ventilation system combining Computational Fluid Dynamics (CFD) with Artificial Intelligence (AI). This predictive model was created to forecast the temperature and humidity evolution of a ventilated room to be implemented in a digital twin for better unsupervised control strategies. To replicate the full range of annual conditions, a series of CFD simulations were configured and executed based on seasonal data collected by sensors positioned inside and outside the room. These simulations generated a dataset used to develop the predictive model, which was based on a Deep Neural Network (DNN) with fully connected layers. The model’s performance was evaluated, yielding final average absolute errors of 0.34 degrees Kelvin for temperature and 2.2 percentage points for relative humidity. The presented results highlight the potential of this methodology to create AI-driven digital twins for the control of room ventilation.