Vance was defending the deal reached this week to end the war with Iran that critics in the United States and Israel have criticised for failing to curb Iran's missile program and providing no clear path to dismantling its nuclear facilities while constraining Israel in its war with Hezbollah militants in Lebanon.
Trump has repeatedly criticised longtime ally Israel, spiking tensions nearly four months after the two countries partnered to attack Iran.
Vance, asked at a White House news briefing about a report that Israeli Prime Minister Benjamin Netanyahu was fuming over the agreement, said he had not heard such comments from Netanyahu but criticised members of the Israeli leader's cabinet, who he said have opposed the deal and personally attacked Trump.
"My message to them would be twofold. No. 1: Donald J Trump is the only head of state in the entire world who is sympathetic to the nation of Israel at this moment in time," Vance told reporters at the White House.
"If I was in the cabinet of the Israeli government, I might not be attacking the only powerful ally that I have anywhere left in the entire world."
He said he would also remind those cabinet members that two-thirds of the defensive weapons that have protected Israel "have been built by American hands and paid for by American tax dollars".
The United States provides Israel with roughly $US4 billion ($A5.7 billion) in military assistance a year but the two countries are negotiating a new aid agreement.
"The problem for Israel is not Donald J Trump and anybody in Israel who thinks their biggest problem is the president of the United States needs to wake up and smell the reality of the situation that country is in," Vance said.
Netanyahu's office and Israel's Foreign Ministry did not immediately respond to a request for comment.
Israeli senior officials, speaking anonymously, have said the deal terms were bad for Israel because they failed to address concerns over Iran's nuclear and ballistic missile program, a view they say is shared across Israel's leadership.
Trump tried to play down Israel's concerns during closing remarks on Wednesday at a G7 summit in France.
Netanyahu could use a "softer touch" in the fight against Hezbollah militants in Lebanon, Trump said.
In his first comments since the deal, Netanyahu said at a public event that Israel appreciated its relationship with the US but would continue to occupy southern Lebanon to maintain security for citizens living near Israel's northern border.
"This requires maintaining the security strip in southern Lebanon; it requires that we not leave there as long as Israel's security needs require it," Netanyahu said.
Israel published a map on Thursday showing an expanded military control zone in southern Lebanon and said it would not rule out carrying out attacks beyond it, challenging the terms of the US-Iran pact.
Israel's ultranationalist National Security Minister Itamar Ben-Gvir, a linchpin in Netanyahu's governing coalition, has harshly rebuked the US-Iran deal and insisted Israeli troops would remain in Lebanon.
Vance criticised Ben-Gvir and Finance Minister Bezalel Smotrich in a New York Times interview released earlier on Thursday.
"What is your exact proposal? You're a country of nine million people. You can't just kill your way out of solving every single national security problem that you have," Vance said.
