My 99 Tahoe with 5.7 Vortec misfires when climbing a long hill or when put under abnormal strain. When back on level, it runs fine.
CE light comes on and codes are: P0300 random misfire detected; P0303 cyl 7 misfire detected & P0430 cat sys below threshold (bank 2)
I seem to be losing coolant internally also.
Have changed plugs and wires.

WHAT is going on?

Could be a blown head gasket. Is there any evidence of coolant in the oil? Check the dipstick.

the 350 is like the 3800 95% of the time its the upper and lower intake gaskets. in fact just about everyone i know with the vortec 350 has changed them once or more. bad part is of you touch the dist you have to take it to someone with a high end scanner have the "cam retard offset" done which the short story is its the timing.

the cat deficiency code is normally the cat because there are different codes for the o2'* being bad.

the misfires could just be the cat, but the other super common (everyone) has to have the POS poppet assembly changed to the delphi mpfi, because the oem one leaks and generally makes the engine run rich and thats primarily what ruins cats

The oil looks normal, not milky. This has been going on for a long time. It runs great except when climbing a hill at highway speeds or after a max effort acceleration. All other driving phases are normal.

I've changed the manifold gaskets twice. Is the POS in the mpfi system the fuel pressure regulator?
I figure the cat problem is related to the misfire just trying to figure out why it misfires.
It runs normal in all phases of driving except when climbing a hill at highway speeds or after a max performance acceleration. This has been going on for a year or so, but seems to be getting worse.

I think the misfires are related to the coolant being sucked in the cylinders. It comes with the territory. If your losing coolant, but its not going in the oil, and you have associated misfires, its intake gaskets.

the oem injectors are called poppets the new style that takes care of most of the issues are mpfi like on a newer car but at the end of a fuel distribution "spider"

the fact that you replaced them before doesnt surprise me, seems common. if you use the good felpro set, clean very well, and make sure you dont tweak the manifolds you should be good. the lower is 83 and the upper is 45 inch pounds, both in two steps. i think some people just crank it down

as far as the coolant in the oil sometimes its hard to tell, i had nothing on my dip stick on this engine and the oil didnt look weird but when i drained it after changing the gaskets the viscosity was like water and when i took the manifolds off there was white crap all over and i got the second valve cover gasket just to do it but i was glad i did because it was nasty in there too.

In that case I agree with Justin and Mike, its probably a bad intake manifold gasket. That could cause all three of your issues; disappearing coolant, misfire under load, and error codes related to the O2 sensor.