MTU and overhead in the service provider space

I'm at the start of my career in the service provider space and know the generalised concept of the lower down the model, the greater the MTU requirement to support the higher layers, but what has always eluded me is knowing how to accurately calculate or configure MTU to take into account the upper layer requirements.

It seems there is such a wealth of combinations to consider in terms of the types of frames, packets and segments that could possibly be transmitted, especially when considering MPLS - how do others seemingly achieve this so easily? Particularly when looking at throughput and the effect of overhead. Is my way of thinking wrong or is there something I'm missing? What helped you all understand this better and are there any great resources available that cover this well?

Thanks.