Boat is a 1980 Scarab with MK IV 454's single 150 gal fuel tank , brand new fuel water separators blower scoops to pull in lots of fresh air. I'm having a issue now where after running for about 8 miles / 10 minutes my port engine is hesitating at higher engine speeds above 3000 rpm. I tried running the boat at 2500 and when it would start to stall I could see fuel pressure drop to 0 at the carb. I thought it was a bad mechanical fuel pump and wired in a Holley red in place of the mechanical pump, but even with the electric pump, fuel pressure was dropping off after about 10 minutes of higher engine speeds. (Above 3000). I thought it was 45 yo fuel lines collapsing so I replaced all of them from the fuel tank to the carb. I also replaced the fuel water separator AND i pulled out the fuel pickup to verify that the tube didn't fall off, also there is no check valve in the fuel line at the tank. The engine oil doesn't smell like gas. The boat starts up great, idles clean and runs great for about 10 minutes, then only the port engine starts to hesitate. Before hesitation, the boat gets up on plane easily. Engine temps with no thermostat are about 145, oil pressure is good, oil temp is about 140, volts are 13. This problem only started this year. Last year in October (In Michigan) the boat ran strong for 16 miles, no issues) this year 8 miles and about 15 minutes total run time and just the one engine starts to hesitate. No changes have been done to the carb. When the engine is hesitating, i can back it down slightly and slowly bring the speeds back up and there is no backfiring. The fuel is fairly fresh, 130 gallons from sams club about 5 weeks ago. anyone else have this sort of problem at high engine speed after running some time?

Also: Ignition is a thunderbolt IV, carb is a Holley 750, no chokes, no filters in carb bowls, flat tappet hyd cam, sea water pump, with a water crossover, water temp runs at 140.

Mine would do the same and I chased it as a fuel issue only because I had the carbs rebuilt by Nickerson performance in the off season. So I thought that it may have been the issue since that was the only change I had from the previous season. I swapped carbs from port to starboard and it did the same thing. I called Nickerson and he flat out told me it's not the carbs and it's an electrical issue and he was totally correct. My ignition module on my thunderbolt IV went bad. It would run great at idle and run good early into a trip and when it got hot, then it would act like a fuel delivery issue and not get above 2500 rpms without hesitation or like it was not getting fuel. Changed the module and everything was good again. I had the opposite ignition module go bad the next year and I did some research on them and found some information on the thunderbolt IV that you need to stick with the Mercury coil. Mine had MSD coils and the resistance is too low and can damage the ignition module. Once I switched to the Mercury coils I never had that problem again.

Good troubleshooting so far. That zero fuel press is the biggest clue.

I'm assuming you don't have fuel press regulators that can bypass.

Maybe there's a foreign object in the fuel tank that gets sucked up against the fuel pickup tube, partially blocking flow under high demand?

I would try running a hose from the Holley red pump output back into the tank or into a bucket/gas can and see what the flow looks like. See if it starts out strong then tapers off after a bit. May need to adj trailer attitude to match running attitude (i.e. bow up) if it's related to foreign object in the tank.

or the fuel tank vent may be clogged causing a vacuum in the tank. take the fuel cap off and see if it changes anything

Fuel vent is wide open. I can feel air coming out when I fill the tank and have no issue when filling it. And since both engines pull fuel from the same tank and I have no issues with the other engine, i feel that this is not the source of the problem.

UPDATE: Ran the boat the other day with a dash mounted fuel pressure gauge. the fuel pressure started out at 7 psi and it stayed consistent at 6 psi. the engine never stalled out but I did notice that the pressure did drop to 5 psi for a bit after cruising for about 20 minutes. Wellcraft put in the wrong fuel pick up and the outlet at the tank is 1/4 npt even though the dip tube is 3/8" Im going to have a pair of new tank pickups made that will be 3/8 stainless tub welded to a 3/8 npt to -8 AN straight fittng. Then Ill connect a -8 90 degree hose end to it. That should be overkill for the fuel pickup. Im also going to replace the existing fuel pump, which im not sure what brand/gph it it is with a Holley 110 gph fuel pump.

Do you have a filter on a fuel inlet?
A 1/4" line is generally sufficient, but a small piece of debris can clog it. I had exactly that issue with a different engine. Everything was working fine, and then the engine suddenly shut off. In the middle of the sea, I had to blow out the fuel line just to get back to the marina.

The cause:
We had replaced the fuel level sender and used regular silicone sealant meant for sealing engine sumps. A small "drop" of that sealant fell into the fuel tank and started causing problems. After installing a simple homemade filter from inox wire mesh, the issue was resolved.

Sam's Club fuel E10. I would recommend not using it and would use non ethanol fuel. Not causing your issue, but running it long term may cause future issues.

The risks I know of with using E10 are it will act as a cleaning agent inside the tank, its harder on the rubber components of the fuel system and if it sits for a while it can go thru phase separation.
My fuel lines are brand new and are rated for alcohol type fuels, the fuel water separator is brand new and the fuel pump is a 2 year old Holley mechanical fuel pump. The lines on the carb are hard line. Im going thru about 150 gallons every 3-4 weeks and I take the boat out for short jaunts weekly. The last fuel water seperator i pulled off had 150 gallons thru it and when I cut it open I didnt find and debris or anything abnormal.
other than the cons Ive listed are there other reasons to not use E10 from Sam's?