Environmental control and life support systems will require enhanced self-awareness and self-sufficiency as human spaceflights are designed to reach further destinations. These requirements have led to the development of autonomous technologies and systems to enable more Earth independence, while at the same time relying more heavily on the knowledge contained in their computational models (as opposed to the knowledge of ground control experts). For environmental control and life support systems, these consist of disparate models often tailored to specific subsystems and use cases, such as temperature control and [Formula: see text] removal. Therefore, there is a need for technologies supporting the integration of existing models. We propose to extend existing digital twin frameworks to integrate models and serve as a tool for answering onboard queries during operation. Toward this vision, we identify research directions for three types of technologies: i) streamlining the process of merging information models without redundancies by leveraging model-based systems engineering languages; ii) the calibration of simulation models that requires a better understanding of how to encode domain knowledge into a probabilistic representation of subsystem states and model parameters; and iii) automating the query understanding process and constructing a mapping between information and simulation models.