Iran's UN ambassador wrote in a letter that any cooperation by third countries with Israel's strikes on Iran "makes them complicit in the legal responsibility and consequences of this crisis."
Israel is "doing what we need to do," Netanyahu said when asked if Israel would target Khamenei.
The IDF also struck an Iranian military base in western Tehran.
The Fordow Fuel Enrichment Plant has enriched a huge amount of uranium to the 60% level, has tremendous enrichment capacity, and is based in Qom Province.
Multiple Iranian weapons and missile launchers were destroyed in the air force strikes.
The strike killed the head of the Revolutionary Guards' intelligence organization and his deputy, as well as the head of the Quds Force's intelligence branch and his deputy.
In the coming hours, Israel is expected to order residents of various neighborhoods in Tehran to evacuate, followed by strikes on infrastructure and government buildings.
The execution is the third in recent weeks related to the conducting of espionage on behalf of Israel.
Israel's Air Force and Navy intercepted over 100 drones fired by Iran so far, with no reports of any that fell in Israeli territory, the military added.
The identity of the two suspects, as well as further details into the investigation, are under an active gag order.