First, these answers insofar as the licenses and airline operations apply to the U.S. system since that is all I am familiar with.
You must have a Flight Engineer license to operate as an FE. Just as a pilot's license has ratings on it, so does an FE license, and you have to have a rating that matches what you're flying. My FE license has a single rating, TURBOJET POWERED, so I could not sit as an FE in other than a jet aircraft.
In the days when 3-man cockpits were the norm, the usual career course at large carriers was to start out as an FE (second officer), progress to being an FO (first officer), and then a captain. In that system, if the FE was incapacitated, it was likely that one if not both of the pilots had actually been an FE.
The U.S military continued with FEs well after the 3rd seat came out of civilian aircraft (I think they still do, but am not sure). Military FEs were typically never intended to become pilots. When all new civilian aircraft being manufactured were 2-man cockpits, but lesser airlines were still flying the old 3-man cockpits (think freight carriers in particular), former military FEs became the source for their FEs and were considered professional FEs, in other words they would not be progressing to a pilot seat. A few did, but they were definitely the exception.
The two 747 carriers I worked for hired pilots into the FO seat. The FEs they hired had to have A&P licenses as well as an FE license, the reason being that the company wanted them to be able to perform and sign off minor maintenance problems that occurred in remote places (think Africa especially) where maintenance wasn't locally available. With only a couple of exceptions, every FE I ever flew with was ex-military with an A&P, and they knew the airplane mechanically better than I.
In the airline ground schools, especially the initial groundschool, the FE panel and its operation were thoroughly covered in the material presented and in the testing. The oral exam for the aircraft type rating thoroughly covered that FE panel. As I remember my 747 type rating oral was 3 to 4 hours long. Fortunately I got through that and the sim ride on the first try. Not all do.
So, in the case of an incapacitated FE in the 10 years I was on the 747, it was likely that neither pilot had actually operated as an FE. However, he would have studied it in ground school and had demonstrated an understanding in an oral exam. There is, though, nothing like experience and currency.
Every once in awhile I would get out to a cold airplane before the FE had arrived and would want to start the APU. This was usually at a remote station without local maintenance. There was, of course, a procedure for doing this, and I had a copy. But even with that check list and doing everything very carefully, I always breathed a sigh of relief when the APU started and there were no problems. If the APU failed to start on the first try, I usually waited for the FE to arrive. I might try a second time if I knew he was going to be awhile, but never a third.
The old 747-100/200 had a lot of switches, and interesting things could happen if the APU was started and the switches were not properly set. I always did an outside check to make sure all gear doors were closed and that nobody was around the bottom of the airplane. If a gear door was down, and switches were not set right, when the APU started, the doors would immediately close when the hydraulics were pressurized. Anyone in the way would certain get hurt.
Individual pilots on the line varied greatly in their knowledge of the FE panel. FOs were at a disadvantage insofar as watching it be operated. They can't see it well. Captains can see it. However, some FEs resented captains looking at it too much, feeling that was their turf. What I often did during cruise, as much to pass the time as learn, was to let the FE be my tutor.