Iranian missiles again evaded Israel's sophisticated aerial defense array on Thursday, striking a main hospital in the south as well as residential areas in the country's populous center.

Israel has long relied on its multilayered missile defense system to protect communities around the country from rocket barrages from militants in Gaza or Lebanon. Since the wars in the Middle East erupted in 2023, that list has grown to include fire from rebels in Yemen and Iran.

For years, Israel has targeted Iranian nuclear scientists, hoping to choke progress on Iran's nuclear program by striking at the brains behind it.

Now, with Iran and Israel in an open-ended direct conflict, scientists in Israel have found themselves in the crosshairs after an Iranian missile struck a premier research institute known for its work in life sciences and physics, among other fields.

If the U.S. decides to support Israel more directly in its attack on Iran, one option for Washington would be to provide the "bunker-buster" bombs believed necessary to significantly damage the Fordo nuclear fuel enrichment plant, built deeply into a mountain.

Such a bomb would have to be dropped from an American aircraft, which could have wide-ranging ramifications, including jeopardizing any chance of Iran engaging in Trump's desired talks on its nuclear program. Israeli officials have also suggested that there are other options for it to attack Fordo in central Iran as it seeks to destroy the country's nuclear capabilities.

Jeffrey Fields USC Dornsife College of Letters, Arts and Sciences

Relations between the United States and Iran have been fraught for decades – at least since the U.S. helped overthrow a democracy-minded prime minister, Mohammed Mossadegh, in August 1953. The U.S. then supported the long, repressive reign of the Shah of Iran, whose security services brutalized Iranian citizens for decades.

Israel stunned and hobbled Iran last week when it pulled off an intelligence and military operation years in the making that struck high-level targets with precision.

Guided by spies and artificial intelligence, the Israeli military unleashed a nighttime fusillade of warplanes and armed drones smuggled into Iran to quickly incapacitate many of its air defenses and missile systems. With greater freedom to fly over Iran, Israel bombarded key nuclear sites and killed top generals and scientists. By the time Iran mustered a response hours later, its ability to retaliate — already weakened by past Israeli strikes — was greatly diminished.

Hezbollah has long been considered Iran's first line of defense in case of a war with Israel. But since Israel launched its massive barrage against Iran this week, the Lebanese group has stayed out of the fray.

A network of powerful Iran-backed militias in Iraq has also remained mostly quiet — even though Israel used Iraq's airspace, in part, to carry out the attacks.

Israeli strikes on Iran on Friday and Tehran's vows of reprisals have brought the two Middle East adversaries closer to an all-out war, which also threatens to draw in the United States, at least to some degree.

So how do the militaries of Iran and Israel stack up against each other?

Israel's massive strike on Iran on Friday morning came after decades of mutual hostility and a long-running shadow war of covert strikes and sabotage.

Israeli Prime Minister Benjamin Netanyahu has long identified Iran as its greatest threat, citing the country's nuclear program, its hostile rhetoric and support for anti-Israel militant groups across the region. Iran has championed the Palestinian cause and portrayed Israel as a malicious Western encroachment on the Middle East.

The outline of the U.S. offer to Iran in their high-stakes negotiations over Tehran's nuclear program is starting to become clearer — but whether any deal is on the horizon remains as cloudy as ever.

Reaching a deal is one of the several diplomatic priorities being juggled by U.S. President Donald Trump and his trusted friend and Middle East envoy Steve Witkoff. An accord could see the United States lift some of its crushing economic sanctions on Iran in exchange for it drastically limiting or ending its enrichment of uranium.

Iran has multiple major sites associated with its rapidly advancing nuclear program, now the subject of several rounds of negotiations with the United States.

The sites across the country, including one in the heart of Tehran, the capital, show the breadth and history of the program. One in particular, Iran's Natanz enrichment site, has been targeted several times in suspected sabotage attacks by Israel amid tensions between the two Mideast rivals.