Nukes wouldn't do shit to their ships. Nuclear weapons are significantly less effective in vacuum. You'd just scorch the paint, even if you managed to get past their ungodly amount of point defence.
I doubt anyone but rogue states would be stupid enough to wheel out nukes when there's a km-long warship hanging in low Earth orbit. Not much of a trade-off if you vapourise a couple of million guardsmen, irradiate your own soil, then have three of your major cities flattened by orbital bombardment you can't respond too.
Lasguns would be significantly better than modern rifles I imagine, at least in terms of accuracy and the amount of shots. Ammunition supply is a big thing in fire fights, it's partly the reason for the shift away from 7.62mm to 5.56mm, you can carry twice as much of the latter.
Given that Necromunda established that guard flak armour is actually pretty top-tier protection against your average stub gun (i.e. what our projectile weapons would be), it suggests the Imperium has considerably advanced material sciences, I imagine the regular guard armour on both their men and vehicles would be extremely difficult for our weapons to penetrate.
Same goes for their aircraft, which given we know they can produce SSTO fighter aircraft, are going to shit all over stuff like the F-22 despite looking like something out of WW2. Plus they could just crater all our runways from orbit. Modern fighters don't do so well on grass airstrips like WW2 fighers did.
We have nothing that could challenge Knights, other than limited air power, let alone void-shielded Titans or Astartes.
We'd have some advantages, our man-portable anti-armour technology is significantly better than the guard's, at least in precision, since all of their weapons are dumb.
But generally, they have ships, we don't, it'd be a curb stomp. We'd have to resort to asymetric warfare and the Imperium isn't touchy-feely 'don't hurt the civilians' like NATO is, so that wouldn't work so well.