That is a true mystery a Dyno reveals. But who has dynoed there engine to know this? A bit can be revealed with the detail of your engine and drivetrain. Every detail must be known for this.
Crane cams list there cams with helpful tips to how & where the cam performs the best. Between your gear ratio & tire size, this should give you a certain rpm at speed.
Let's say your normal cruise mph is 75. What is the rpm? Does it fall somewhere within the range of cruise listed?
If you have a desk top Dyno coumputer simulation program, you can get a decent idea. While it is not a great substitute for a actual Dyno test, it is pretty good.
Making sure your engine is running its best through out the rpm range is a trick and a half with a carb. (F.I. takes care of that.)
I think that tuning your engine to run best at 3500 isn't going to help a ton if your cruising at 2600. As allways with drag racers, it is so with everything else for regular guys just putting down the Hwy. chances are your not making the most of your combo for the drag strip or the Hwy.
Just tune tune tune your engine at your Hwy. speed and you will be fine. Make it as efficient as possible.
Most street engines have a broad long flat torque curves. This is what a regular street engine should have. Stock or modified. When the torque curve becomes more peaky you have a harder time in that narrower range to tune and cruise in.
Of course, turning 3500 @ Hwy. and being super tuned isn't going to get you high mileage.