The unpredictable president arrives having already upturned expectations when it comes to the decades-old Middle East conflict, giving Palestinians more hope than they may have anticipated and disappointing right-wing Israelis who heralded his election.
He has spoken of reaching "the toughest deal to make", one that has long bedevilled US presidents, vowing "we will get it done".
But he is also contending with a raft of problems back home, including a special counsel investigating whether his associates colluded with Russia.
Beyond that, Trump has faced criticism from Israelis in recent days related to the White House's approach to the ultra-sensitive status of Jerusalem.
Concerns have also been raised over Trump's sharing of intelligence with Russia said to have originally come from Israel.
"I think the trip's in a lot of jeopardy being able to be productive because of all the chaos and controversy that's going on in Washington," Dan Shapiro, US ambassador to Israel under Barack Obama and now a senior fellow at Tel Aviv's Institute for National Security Studies think tank, told AFP.
He is expected to become the first sitting US president to visit the Western Wall, the holiest site where Jews can pray and located in east Jerusalem, which Israel occupied in 1967 and later annexed.
Israel sees all of Jerusalem as its undivided capital, while the Palestinians view east Jerusalem as the capital of their future state.
On Tuesday, he visits Bethlehem in the occupied West Bank for talks with Palestinian president Mahmud Abbas.
Trump has sent mixed signals about how he will approach the Israeli-Palestinian conflict.
He cast uncertainty over years of international efforts to foster a two-state solution when he met Netanyahu at the White House in February.
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