I think there is one more step change theoretically possible in terms of energy output which is based on anti-quark collisions. We need to understand QCD better. Its hard to know when breakthroughs will happen. Maybe its already happened and we just havent heard about it yet!

We also dont know how to model quantum gravity still. That seems pretty fundamental.

Im optimistic there will be physicists who find something new and whacky that no one could predict.