Pizza Express is taking on the city centre site left behind by the former Potted Hen restaurant.
The restaurant chain is opening two new locations in Belfast, including another in Ballyhackamore in the east of the city, which is also set to welcome a new Caffe Nero.
Mark Thallon of TDK, the property agency behind the new east Belfast development, said the city's food and drinks sector was "undergoing a renaissance".
The latest Pizza Express location in the city centre will sit opposite homegrown Italian restaurant Coppi, at the site vacated by the Potted Hen.
The restaurant was opened in November 2010 by chef Dermot Regan and his wife Catherine, who had already tasted success with another eatery, Oregano in Newtownabbey, which is now also closed.
It was also where a dissident republican bomb exploded in December 2013.
Financial difficulties began for the couple in March 2014 when the company that owned Oregano was the subject of a winding-up order.
The husband and wife team were directors of the firm.
Then, last year, an insolvency order was brought against Mr and Mrs Regan, both from Lower Rogan Manor in Newtownabbey.
The restaurant continued to trade, albeit under a different limited company, before it suddenly closed its doors in October last year.
UK-headquartered Pizza Express, which is owned by Chinese group Hony Capital, has three Belfast restaurants, including one in Victoria Square.
The Italian chain's new east Belfast spot on the Upper Newtownards Road was rumoured to be the location for Jamie Oliver's first restaurant in Northern Ireland.
Alterity Developments and TDK Property have also announced a new Prezzo Italian restaurant at the Boucher Square development, which already has a Costa Coffee, Ed's Easy Diner and Frankie and Benny's.
Mark Thallon from TDK told the Belfast Telegraph: "We have been absolutely delighted with the success of Boucher Square, which has meant us having to look at ways to try and meet the demand for operators wanting a presence."