Images and data representing morphology, function, and metabolism are medically produced in the scope of specific protocols and pathologies. Although generally assessed individually, these data can also be merged together into a multidimensional digital space that simulates the reality of the patient from many different perspectives. This space can then be navigated at will along any dimension, not only for diagnosis but also to plan, simulate, or monitor surgery or other types of therapy. These approaches can be used for addressing various research or clinical needs such as the primary and secondary assessments of complex pathologies, including cancer and epilepsy. Concepts such as those presented in this article represent an adequate foundation not only for an optimum exploitation of all available information for in-vivo assessment and therapy guidance but also for a more effective assessment of the full scope and requirements of live systems simulation(s) accurate enough for supporting clinical and research developments.When dealing with computers and real-life processes, simulation generally conveys the connotation of a physics (or otherwise)-based mathematical model intended to imitate or to predict the appearance or behavior of its real-life counterpart. In medicine-and even more so in diagnosis assistance or therapy planning-simulationlike approaches are becoming ever more essential and most often rely on digital representations of the patient from clinical imaging data sets. Although such simulated entities could sometimes be entirely virtual (i.e., with no real patient attached), this article will concentrate on the use of simulation-like techniques to help in diagnosing or treating complex pathologies for actual patients. In the core of this article, simulation, virtual model, and digital representation (DR) of a AUTHOR'S NOTE: Thanks to the Department of Radiology for clinical magnetic resonance imaging, single photon emission computed tomography, and positron emission tomography images; the Clinic of Neurology for clinical electrophysiology data (electroencephalography [EEG] and spherical electromagnetic tomography [EMT]); the EEG and Epilepsy Unit for overseeing clinical epilepsy investigations; and the Clinic of Neurosurgery for all surgery (including invasive implantation). Data collection, merging, and all other processing and visualization performed in the Laboratory of Functional and Multidimensional Imaging. Also a special thanks to David Crookall for his valuable advice in making this article more suited to its intended aim.