President Joe Biden is on his way to Israel for one of the most complicated diplomatic trips of his presidency, an extraordinary high-stakes trip to a region gripped by violence in the aftermath of Hamas' attacks and Israel's subsequent response.

Biden's arrival in wartime Tel Aviv Wednesday will mark his most forceful public show of support for Israel since the October 7 attacks by Hamas that left 1,400 of Israelis -- and dozens Americans -- dead. Other Americans, along with many Israelis, are also being held hostage by Hamas. And at least 3,000 people have been killed in the Gaza Strip since the fighting began, the Palestinian health ministry in Gaza said Tuesday.

Biden's arrival in Tel Aviv will come hours after a horrifying blast on Al-Ahli Baptist Hospital in Gaza City on Tuesday. Palestinian officials have said hundreds are dead following the explosion at the center of the city and blamed Israel. The Israelis denied responsibility and pinned blame on a failed rocket launch by Palestinian Islamic Jihad.

The hospital explosion caused a scramble of Biden's plans for the trip as the president walked onto Air Force One. The president was expected to meet King Abdullah II of Jordan, President Abdel Fattah el-Sisi of Egypt and Palestinian Authority President Mahmoud Abbas to discuss a humanitarian response during the Jordan leg of the visit, but the summit -- and the Jordan leg of the trip -- was scrapped. The White House cited a period of mourning announced by Abbas as the reason for the postponement.

Israel has provided the US with intelligence it has gathered related to the deadly explosion, according to an Israeli official and another source familiar with the matter. The US is analyzing it and administration officials have communicated that message to at least some congressional lawmakers, the source familiar said. The explosion led to a last-minute briefing by the president's top national security advisers and a phone call with Secretary of State Antony Blinken, still traveling in the Middle East, to assess the intelligence available. But no conclusion was drawn about who was behind the blast, CNN has learned, with the president instructing his team to continue evaluating the available information.

The explosion and subsequent blame game will hang over Biden's meeting in Israel, where he is expected to meet face-to-face with Prime Minister Benjamin Netanyahu and other top officials. The presence of Biden, who places a premium on personal diplomacy, is meant to show solidarity with the United States' closest allies and to deter rogue actors in the region from opening up a second front in the war.

The president has been attempting to walk a fine line between supporting Israel and keeping the violence from spiraling into a wider military conflict, a mission made more complicated by the hospital blast. He and other US administration officials have been warning other regional players, namely Iran and its proxy Hezbollah, from expanding the fighting further.

Biden will first meet with Netanyahu for a restricted bilateral meeting, National Security Council spokesman John Kirby told reporters aboard Air Force One in a preview of Wednesday's trip. That meeting will broaden to include other US officials and the Israeli War Cabinet.

In those meetings, Kirby said, "He's going to get a sense from the Israelis about the situation on the ground, and, more critically, their objectives, their plans, their intentions in the days and weeks ahead."

Biden "will be asking some tough questions. He'll be asking them as a friend -- as a true friend of Israel, but he'll be asking some questions of them." Pressed later on what those tough questions would be, Kirby said it would not be "adversarial" but rather, "in the spirit of a true, deep friend of Israel."

Biden's focus will be on managing a complicated situation and less on securing clear deliverables, according to two sources close to the matter -- a clear sign that the White House is seeking to manage expectations after the Jordan portion of the trip was scrapped.

While violence such as the hospital blast was always seen as a possible risk of the visit, the president's team concluded that the merits of the trip outweighed those risks. Multiple sources told CNN that the president's top advisers did not come close on Tuesday to canceling the Israel portion of the trip.

Israel readies its next steps

The high-stakes diplomacy while on the ground will be closely watched as Israel prepares its latest response to the Hamas attacks. While Biden largely refrained from calling on the Israeli government to use restraint in the days following the attack, he warned the Israelis against occupying Gaza during an interview with CBS News' "60 Minutes" that aired on Sunday.

Israeli Ambassador to the UN Gilad Erdan told CNN's Kaitlan Collins earlier this week Israel has "no interest" in occupying Gaza.

Israel has been signaling it is preparing for a ground invasion of Gaza, even as a humanitarian crisis grows inside the coastal Palestinian enclave. Biden has called for the protection of civilians, and the United States has been working to alleviate shortages of food, water, and gas. Biden said in the interview he believes that there needs to be a humanitarian corridor to help civilians trapped amid the fighting and that Israel will abide by the "rules of war."

"I'm confident that Israel is going to act under the measure ... the rules of war," Biden said in the interview. "There's standards that democratic institutions and countries go by. And so, I'm confident that there's gonna be an ability for the innocents in Gaza to be able to have access to medicine and food and water."

American officials want humanitarian plans for Gaza fully signed off on and implemented before start of the invasion, multiple people familiar with the matter told CNN, describing that task as among Biden's main objectives during his visit to Tel Aviv on Wednesday.

"We want to see humanitarian assistance flow in -- and it's not just a one and done -- we want to see it be able to be sustained: food, water, obviously electrical power, medicine, all the things that the people of Gaza are going to continue to need as this conflict continues to go on. So he'll make that case very, very clearly," he said.

While many Americans feel deep sympathy for Israelis in the wake of the attacks, according to a CNN poll released Sunday, Biden also faces political pressure at home over how he responds to the attacks and how much support he offers Netanyahu's government. Americans are split on whether the Israeli government's response to the attacks are fully justified, including just 38% of Democrats, according to CNN's poll.

The same poll shows the public is mixed over how much trust it has in Biden to make the right decisions on the fighting between Israel and Hamas -- 47% have at least a moderate amount of trust. And about half of Democrats are also feeling a lot of sympathy for the Palestinian people who are feeling the brunt of Israel's response to the attack, the poll shows, which could further complicate Biden's decision-making on how much support to provide the Israelis.

Biden deeply affected by the conflict

The president and other officials have said the US has no plans to put American boots on the ground at this time. But roughly 2,000 US troops are preparing for a potential deployment to Israel to help with tasks like medical and logistical support, multiple defense officials said.

The decision to travel to Israel so soon after the Hamas attack signals just how affected Biden has been by the violence in the region.

Advisers to the president told CNN that the days after the attack were a deeply emotional time for him, as he grappled with the second major outbreak of a war during his presidency and as the images and stories of Hamas' reprehensive actions poured in.

During his trip, Biden will meet with some families impacted by the violence of the past week, including some who have lost loved ones in Israel, and some who "still don't know the fate of their loved ones," Kirby said. Some of those family members have loved ones who are being held hostage, though it was not immediately clear whether they are Americans.

But despite ongoing discussions with Israel and other partners, sources downplayed the expectation that the visit would result immediately in a refugee deal or the release of American hostages in Hamas custody.

The president spoke forcefully throughout the week about his horror at Hamas' actions, frequently comparing the violence to some of the things European Jews experienced during the Holocaust. Biden has taken family members on trips to the Dachau concentration camp to learn about horrors of the Holocaust, and he emphasized in the "60 Minutes" interview how important it is for the world to learn about past persecution of the Jewish people.

"The Jews have been subject to abuse, prejudice and attempts to wipe them out for, oh, God, over a thousand years," Biden told interviewer Scott Pelley. "For me, it's about decency, respect, honor. It's just simply wrong. Wrong, wrong, wrong. It violates every religious principle I have and ... every single principle my father taught me."

The president's interactions with his Israeli counterpart will also be closely watched. Biden and Netanyahu have known each other for decades and have relied on that history as they weathered deep strains over the past year related to Netanyahu's far-right governing coalition and judicial overhaul plan. Biden believes he knows Netanyahu "better than anyone," one official said, and in the past has carefully applied pressure on the Israeli leader to avoid inflaming or escalating conflicts with the Palestinians.

It's also the second time the president has visited a nation at war this year, following February's surprise trip to Kyiv. While Biden previously made visits to Iraq and Afghanistan during his time as vice president, the trips to Israel and Ukraine posed a unique security challenge without as much US military control of the area.