As much as possible the US wont enter Syrian airspace to avoid getting shot down. F22 is designed for air superiority and its ground attack capabilities are just basic. It means it needs to enter Syrian airspace in order to get a shot. Unlike F15 Eagle E, will just fly outside of the Syrian Airspace and fire a long range missile to hit the target.
But the likely scenario really if ever the US attacks is by tomahawk cruise missiles ( or even B2 Bomber 1 sortie)
It would be Tomahawk vs Pantsir S1 + Buk M2
