Can this operate over Syria without getting shot down? Possibly not, right? Maybe over Iraq since it still has no defensive capability but it has to get past Syria first. Even with Syrias degraded capabilites, a large air refueller like that would be a target and Syria will take shots at it for sure.
It is quite possible that the last mission that Israel did against Iran, was from buddy-refuelling from other stealth jets, thereby allowing to reach the required range while maintaining a stealth cloke to allow some level of operational military capability. If so, then that approach will limit the amount of military capability it can bring to the table due to the need to maintain the logistics of the operation and the small number of stealth jets that Israel has at 39 F35s to date. if 1 jet is used as a fuel muel to get to the target and 1 to get back safetly, then if all F-35s are operational, Israel can at most put 13 F-35s on target. If Israel can operate F15s over Syria and Iraq in a contested environment as fuel-muels, then Israel can put more F35s over the targets.
Given the risks involved, it does seem to suggest a route via the red sea. It means that while aircraft can reach Iran via that route, the combat missions will be long and they will be limited by Israels aerial refuelling capability interms of how many planes it can have on target ( assuming of course that the Americans do not provide "logistical support" ) and the payload it can carry there. Are bunker-busters possible to deploy over those distances given the fuel requirements for ordinance of that size and weight ?
The key barrier to this operation is the logistics to operate an air campaign over Syria/Iraq or the Red Sea. Can Iran hunt down and destroy aerial refuellers??? Does it have the fighters with the range that allow it do that, and that with the required level of intelligence capabilities to locate such assets. If Iran does go for the refuellers, with the Americans shoot down Iranian Aircraft as part of "defending Israel". Focussing on the weak point of Israels operation ie air-to-air refuelling capabilities is what will allow Iran to undermine the attack. That is why having planes like Su-35s/30s are so useful to Iran if it has managed to take delivery of some of them. Even better, Su-57s which would be significant risks to any operating air refuellers though that is one for the future.
We have to for now assume the Sultan of Istanbul will not "allow" Israel to transit its airspace on a mission to attack Iran and will "actively" contest any presence of the IDF over its airspace.
The Yemen route, while poseing some operational logistical issues, is a safer route as Yemen has only been able to shoot down drones so far and not jets ( though they could successfully take a pot shot at an aerial refueller if it came in range).
Israel has serious logistical issues in mounting its operation because when it said "we expect our local allies to help, most of the local allies have so far given the middle finger back in reply to Israel". Getting the middle east countries on side with Iran has been key to limiting Israels choices of attack. It also serves those middle-east countries interests by reducing the possiblity of an all out war, where their infrastructure is at risk from an angry Iran.
Syria and Iraq are key to Israels ability to contest with Iran, so you can see why Israel has been so determined to undermine both countries militarily and economically to date.
Lets see. Israel will reply, but i suspect the scope and size of the reply will be limited by logistical issues and targets will be selected to create the biggest theatrical bang for the buck visual experience rather than a real sustained campaign.
It will be interesting to see what Israel can pull of "alone", and what the USAF will do as part of supporting "Israels right to defend itself" interms of logistical and intelligence support. I do expect a naval/submarine dimension to this due to the logistical issues involved.
All of the above only holds true if the Arab countries do not team up with Israel and USA to attack Iran of course.