Into the weeds engine design for fuel efficiency discussion.

There's lots one can do to old engines to get them closer to modern consumption.

Looks at late model engines and the trends are clear:

Smaller ci will always improve mpg. Smaller bores burn more completely. Shorter strokes lose less to piston friction. There's a reason for so few big-bore engines outside specialty vehicles.

Thinner rings and lower ring tension, which requires more precise bores, BTW. Better chambers, but also lower crevice volumes - so you want head Gaskets with bores that nearly match the block, high upper rings, etc. The valve job will probably have more effect than the exact shape of the chamber. Squish, quench, whatever you call it does matter but with a reasonable compression ratio (9.5-11, imo) it'll happen anyway so it's not worth sweating over.

Then there's the lubrication side.
Thinner oil is easier to pump, better lubrication and solid films on piston skirts help reduce friction too.

High static compression improves efficiency and requires precise timing control and octane requirements, which is where knock sensors come in. High compression can increase pumping losses though, and so the exact right ratio will depend on the cam to a great extent.

You can reduce pumping losses by closing the intake late but obviously this can also kill torque down low, which is where variable valve timing comes in. Without it, you get to pick either a high torque under 5k, or a screamer that has to cruise at 3500. Similar to the lower ci deal, lower revs will always use less fuel so choose your operating rpm range wisely. A low peak power rpm will come with a low HP number too. Built right, you'll be able to sustain highway speeds uphill no problem, but your 0-60 is probably going to be double digits even with no load or trailer.

Even the cooling system is a huge deal. I remember an ASE article circa 2005 talking about molded plastic coolant diverters that Audi was putting into their open deck cooling jackets to even out the temperature of the cylinder wall. They realized something like a 4% reduction in consumption across the power band due to better ring seal. Also, hotter temperatures tend to operate more efficiently but are also less tolerant of mistakes. 205-215deg thermostats are not uncommon in modern engines. Also, dual acting thermostats, which my or my not be adaptable using an external housing on a Mopar v8.

Fuel delivery is a whole book unto itself. Port injection is a great compromise because it's still far enough from the valve to cool to intake charge and atomize the fuel, but not so far as to cause a lag in mixture correction when conditions change (passing, or sudden additional commanded power) and not so close as to wash the cylinders down or cause valve deposits. Having injectors in the ports also makes it possible to trim each cylinder individually.

We can also posit that additional mpg and efficiency could be found in reducing reciprocating mass like the rods and pistons. The OEMs don't make them thinner and thinner each year just to save on metal costs alone..

Reducing rotating mass can help, but less so than reciprocating masses. But every single time a car accelerates it has to spend energy getting the crank and flywheel and trans up to speed again.. So they do still matter.

Speaking of transmissions. There can be a lot of sophistication built into them beyond just a lockup converter and extra gears. Newer transmissions do the job far better than any of our old hot rod parts.

Its not an easy task to accomplish a lot of this. It takes either tons of experience or learning a ton of the math that's already been developed. You'd have to pick the brain of an automotive Engineer to even start finding resources on that. Eng-tips.com often has plenty of gray beards willing to tell you all about many a subject, so that may be a good place to search out info.