The 321-room hotel within the bayside casino and entertainment City of Dreams complex opened to the beat of traditional drums and shower of gold and silver confetti.
De Niro and his Nobu Hospitality partners, renowned chef Nobu Matsuhisa and Hollywood producer Meir Teper, led the ribbon cutting with Australian billionaire James Packer and Macau tycoon Lawrence Ho, co-chairmen of the complex operator Melco Crown Entertainment.
The Oscar-winning actor says he is not only lending his name to the project but is personally involved in it.
"I've looked at what everything is, I am aware very much about the design, and so on and if there's anything I don't like I say it," de Niro said in an interview.
"To me you have to do more than lend your name, you gotta be there in order to just be more a part of it and really believe in it," he added.
Nobu Hospitality will open eight other Nobu city hotels in the next two years, said Trevor Horwell, chief executive officer.
The first Nobu Hotel opened in Las Vegas in 2013 in a venture that evolved from Nobu Restaurants.
De Niro said the hotel was part of a vision sold to him and his partners by Ho and Packer. He said it's going to draw people and eventually help the Philippines.
"(Ho and Packer) are both great visionaries so we felt very comfortable they looked very carefully at the market," Horwell added.
The hotels planned in the next two years are in North America, the Middle East and London. Nobu wants to grow more in Asia, but will do it selectively, he said.