Some 50 countries are to attend the talks, with Palestinians hoping for USD 4 billion in global pledges, despite wariness from donors that without a full peace treaty with Israel they may just be pouring money down the drain.
"I think it's very fair to say that there are serious questions being raised by a lot of the donors about... How best to break this cycle" of violence, a senior State Department official told reporters before Kerry left Washington.
Kerry will also have a series of bilateral meetings on the sidelines of the conference, likely to focus on US efforts to build a coalition against Islamic militants who have seized territory in Iraq and Syria.
The donor conference has been called to seek help for the Gaza Strip as Palestinians seek to rebuild their lives after a 50-day war with Israeli.
Many "had their homes bombed out and have been suffering under very difficult humanitarian conditions for the last several months," the US official said. The conflict killed some 2,200 Palestinians and 73 on the Israeli side.
But amid fears donors will fall short of the $4 billion being asked for, Kerry will use his keynote address to again plead for an end to decades of violence between Israel and the Palestinians by reviving peace talks.
Kerry's own single-minded and dogged pursuit of a long-elusive peace treaty collapsed in acrimony in April after a difficult nine-month process, and there is little prospect of fresh talks any time soon.
Indeed, the Palestinian Hamas militants, who run the Gaza Strip, and Israel have yet to translate their temporary August truce into a permanent ceasefire.
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