The physical substrate upon which we run the simulation will play an important part. For complex high-fidelity simulations that are run on advanced quantum computing systems - we might get some level of fractal-parity going on. Namely, that the "depth" of N-number of simulations wouldn't matter.

There's something in quantum information theory called the Church–Turing–Deutsch principle (CTD).

If CTD is true, then we get a strange phenomenon. If a quantum information system (QIS) can be simulated by another QIS to 100% completeness, than the simulation is indiscernible from reality - at least from the 'inside.' The simulation and the 'base-reality' are subjectively complete to an observer in either system, and thus are indiscernible. It turns physics into a computer science.

Think of a fractal, you can keep zooming in or out, you never reach the top or the bottom, and the features stay pretty much the same no matter how "deep" you go. An advanced civilization would probably be capable of making such advanced simulations, probably with the aide of blackholes or other exotic objects in space.

In the meanwhile, Civilization 6 is coming out in a few weeks. :)