Will a high quality preamp really make a difference in sound?? Also speaker cable

Yes to both

I think the preamp is the most important component in the chain.   I usually spend over budget when I replace a pre so as not to make a lateral move.  

Unless you've had a world class preamp swapped into an already good system. It's hard to explain how pronounced of a difference it CAN be.  May take trying a few but a great one can really elevate your system to a different level. 

What improvements are you looking for, what equipment and cables/interconnects are in your system now, what’s your budget, and are you looking for new or used?

You can’t fix a crappy amp with a better pre-amp the same way you can’t fix a crappy pre-amp with a better amp. Every component plays a role formulating the end result. The key is to get a clean sound signal from start to finish. Quality cables transfer the signal between interfaces without introducing noise or loss. The bottom line is crappy in, crappy out.

I agree with @oddiofyl that a good preamp is of paramount importance and a hard thing to get right. Simple tube circuits are the best solution I've found personally.