Well, I don't have a different cam, heads or intake swap, but I used a tuner out of San Antonio who uses HP Tuners (Nelson Performance). I have it at home too, but don't really know how to use it so I let him tune it. He was able to do everything I needed and has worked on the new LT motors for a friend of mine who recommended him to me. I think it completely depends on your tuner. Some are just affraid to touch it because they don't know about the LT motors, others are familiar with certain ECMs and prefer to stick with those. I have absolutely no problems with mine, but we'll see if it stays like that if I go with a bigger cam later.
Edit: I have headers, and a larger intake tube that messed with the MAF sensor. Took a bit of tuning to get the MAF tables right based on the larger tube diameter, but it all worked out fine. He even gave it a "performance tune" to up the power and run on premium fuel. I don't think it should be very difficult to tune all of those things into this ECM, but then again, I'm not the one doing it.
Good luck!
Oh, and no, it doesn't control the fans. There is a setting in HP Tuners that my tuner turned on, but I don't have wires in my harness for it. I know this ECM is used on a few 4 cylinders that have fans in them, but I haven't tried to run it that way. I just use a Dakota Digital fan controller hooked up through my DD OBD-II BIM module for my gauges.