I would assume that if you are able to go with a later model engine you have to bring its whole "system" with it, meaning the ECU, transmission, catalytic converter, etc. And that would be a major challenge.
With Bill's help (85lebaront2) I was able to effectively put a '96 CA-spec 460 with its EEC-V ECU in Big Blue, and plan to do the same with Dad's truck. But we had wiring diagrams and understood what circuits the ECU thought to be absolutely mandatory.
So if I were to attempt that with something like the 3.5L EB that's in my '15 F150 I'd buy a complete parts truck and also lots of documentation, including the factory shop manual and EVTM. But I'd also want to find someone(s) else that had done it before to lean on as it would be a serious undertaking and there would be a whole lot of head scratching. However, when it was done you'd have a MUCH stronger truck.
Gary, AKA "Gary fellow":
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Dad's: '81 F150 Ranger XLT 4x4: Down for restomod: Full-roller "stroked 351M" w/Trick Flow heads & intake, EEC-V SEFI/E4OD/3.50 gears w/Kevlar clutches
Blue: 2015 F150 Platinum 4x4 SuperCrew wearing Blue Jeans & sporting a 3.5L EB & Max Tow
Big Blue: 1985 F250HD 4x4: 460/ZF5/3.55's, D60 w/Ox locker & 10.25 Sterling/Trutrac, Blue Top & Borgeson, & EEC-V MAF/SEFI