S10 axle will hold up just fine. You will find that any engine you install other then a 235 will have a low mount water pump. This places the fan blades below the bottom tank of the radiator. If you raise the engine to center the fan, you then will need a hump in the floor to clear the transmission. If you choose to alter the floor, your pedal arrangement will need altered some. Before making any drastic moves, set in the truck for a while and get a feel for the lay out. Think about pedals, steering wheel, gear shift, and seats, and try to imagine setting there for a couple hours of driving.
I added a hump in the floor of my '37 which moved the throttle pedal, which then moved the brake pedal. I now have one foot on each side of the steering column and wish I would have done it differently and kept the stock pedal locations.
Theres plenty to think about when swapping parts, so think ahead before moving ahead.