President Joe Biden arrived in Israel under heavy security on Wednesday as he visits the war-torn region on a high-stakes diplomatic trip.

His visit comes a day after a deadly explosion at a Gaza hospital killed at more than 500 people, according to the Palestinian Health Ministry.

The White House said Tuesday evening that the death toll resulting from Hamas’ initial attack in Israel had risen to 31 Americans killed, with 13 Americans still unaccounted for.

The update came from press secretary Karine Jean-Pierre and spokesman John Kirby, during an audio-only briefing aboard Air Force One while en route to Israel.

Meanwhile, the U.S. is planning is impose new sanctions on several Hamas leaders this week, according to a U.S. official.

The Treasury Department is planning to announce the sanctions sometime this week, the official said. The Treasury Department declined to comment.

Earlier Tuesday, a top Treasury official pledged that his agency would “bring our tools to bear against Hamas’ financing and the overall funding of terrorism.”

“Disrupting Hamas’ financing operations is not new to us; this has been a priority for Treasury for decades,” Under Secretary for Terrorism and Financial Intelligence Brian Nelson said at a conference. “We are equipped to target this infrastructure and its supporters, whether they be political leadership, operatives, facilitators, financiers, investors, or entire global procurement networks.”

The Israel Defense Forces have again called on residents of Gaza City to evacuate.

"The IDF calls on #GazaCity residents to evacuate south for their protection," read a post on the Coordination of Government Activities in the Territories X page (formerly Twitter) early Wednesday morning local time.

Col. Elad Goren, head of the Civil Department at COGAT, said in a video message that humanitarian aid will be sent to the areas they are asking people to evacuate to "if necessary."

"In recent days, the IDF has been calling on the residents of the northern Gaza Strip to evacuate their homes and move to the south of Wadi Gaza," he said in the video post shared on X. "This measure was taken to protect them. We recommend moving to open areas in western Khan Yunus and if necessary international humanitarian aid will be sent there. Hamas is trying to prevent the population from evacuating northern Gaza."

Maps were shared in the post, showing where the IDF wanted people to move.

An official briefed on President Joe Biden’s arrangements told ABC News that planning for an Israel trip began more than a week ago when the idea seemed highly unlikely.

The planning proceeded throughout the week and into the weekend, and the agency went through various permutations and contingencies, taking into account different location possibilities and the amount of time Biden wanted to stay in the region.

A spokesperson for the U.S. Secret Service said, "While there will be an immensely intricate security plan implemented in coordination with our military, State Department and Israeli partners, we are not in a position to comment on specifics of the movement."

-ABC News’ Josh Margolin and Luke Barr

The death toll resulting from Hamas’ initial attack had risen to 31 Americans killed and 13 still unaccounted for, said White House National Security Council spokesman John Kirby while aboard Air Force One Tuesday night.

Kirby also said President Biden will have a chance to "meet with some of the families. It'll be some of the families of those who have lost loved ones in Israel, and some of the families who still don't know the fate of their loved ones. And in fact, some of the family members, we expect, will also be family members of hostages that we know Hamas has taken."

-ABC News’ Ben Gittleson

Israeli forces are "preparing thoroughly for the next step -- a multilateral operation in the air, ground and sea," Israeli Defense Minister Yoav Gallant said Monday.

To the soldiers, Gallant said in Hebrew, "Keep preparing for our operation, it will come soon."

"Do your work, get ready," he said. "We will need you.”