Although, there are no physical limits to the size of your model, there are practical limits and hardware limits.
The practical limits are generally related to run time. We all want the model to be a little bit bigger or more detailed. However, that little extra detail or slightly smaller grid size can quickly lead to long run times.
The physical limits are generally related to memory size. If you model requires more memory than is physically installed on the computer, then the computer will start to swap data to the hard disk. This will vastly slow down your simulation.
If your model reaches the practical or physical limits of your computer, then critically evaluate your model to see if you really need such a large, complex model. For example, maybe you can reduce the number of UZ nodes or increase the grid size.
If the model is simply too slow, then you may be able do an initial rough calibration with a less complex model. For example, during the initial calibration, you could double the grid spacing, or shorten the calibration period. Afterwards, you can switch back to the original configuration for the final calibration. You might even be surprised that the rougher model is actually good enough.