Mr Key will be front and centre on the international stage, with a one-on-one meeting with United Nations Secretary-General Ban Ki-Moon and a speech to the General Assembly, but most interest will focus on an opportunity to meet United States President Barack Obama.
The pair have talked by phone but the chance to chat and shake hands at a function the President is hosting will be the first meeting.
"I will reaffirm to him to him that we are very pleased with the way the relationship is going," Mr Key told NZPA.
"That I think it is improving and that's a positive sign I think for both countries."
If he has the chance he will remind Mr Obama of the importance of a trade agreement and the outlook in Afghanistan, where New Zealand has troops.
Mr Key's week kicks off with a UN event on climate change hosted by Mr Ban as he tries to galvanise political will to make serious commitments so a meeting in Copenhagen in December can progress.
He has also been invited to attend a Clinton Global Initiative event which Mr Obama and former president Bill Clinton will attend followed by a meeting.
"It's an economic focus...it will be really interesting to get a stocktake of exactly where the United States sees things at the moment," Mr Key said.
"I think we get a sense that around the world confidence is emerging albeit that it's on a very fragile base.
"But it will be interesting to see what ideas are presented. In particular what the attitude is towards trade, and potentially resolution towards (the Doha trade round)."
The global economy will be a hot topic with the G20 leading economies meeting in Pittsburgh, Pennsylvania tomorrow.
Australian Prime Minister Kevin Rudd is attending that meeting, and will have a quick talk with Mr Key beforehand.
"It's been quite useful because he's tended to give an Australasian perspective, and also a debrief after the meeting so he's been a good friend in that regard."
New Zealand would urge progress on the Doha round of trade talks and progress on climate change.
In his address to the General Assembly at the end of the week Mr Key would focus on New Zealand's continued commitment to the UN, multi-lateral diplomacy, and climate change.
Mr Key will also attend a UN Security Council meeting on disarmament and non-proliferation, chaired by President Obama.
"I think this is a great area where New Zealand can punch above its weight. We've been a leader in being a non-nuclear country and it's an area President Obama raised with me."
New Zealand may host a non-proliferation conference next year, Mr Key said.
While in New York, Mr Key will also catch up with former Prime Minister Helen Clark, who now heads the UN Development Programme (UNDP).
They would talk about aid, the Pacific and have "a natter about domestic politics".
"I think one of the nice things about politics is you do have to compartmentalise aspects of that process, and while we were great adversaries in the political process right up until her departure in Parliament I think once she stood down as leader I worked as aggressively as I could to help support her candidature at UNDP."
Other events include meeting business and expatriates, ringing the bell at the stock exchange and dozens of bilateral meetings including with the head of the North Atlantic Treaty Organisation, and leaders of Turkey, the Netherlands, Israel, Chile, Norway and Rwanda.
Mr Key is also lined up to appear on the popular TV programme The Late Show with David Letterman while he is in New York.
Associate Minister for Climate Change Issues Tim Groser is attending climate sessions and Foreign Minister Murray McCully will attend Commonwealth meetings.
