The Fitzmaurice Street venue first opened in 1857 as the Commercial Hotel and last changed hands after previous owner John Hussey put the landmark up for sale in 2015.

It was relisted for $4.25 million after passing in at auction in April 2016 before being placed into voluntary administration and eventually selling to the current owners.

Following the extensive refurbishment, the pub now has an annual revenue of around $3.2 million.

Continued unsolicited interest from prospective buyers has prompted the hotel's listing on the market, owner Gareth Collins said.

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"Whilst we're more than happy to continue operating the hotel, we have received several unsolicited approaches to acquire the hotel after the last six months and thought we should test the market with a formal process," Mr Collins said.

William Farrer Hotel publican David Barnhill said Romano's would generate a lot of interest.

"Wagga is one of the best pub towns in NSW so I think there will be a lot of interest as proven by the recent activity in Wagga hotels," he said.

"Romano's is one of the most iconic buildings in Wagga, it's is going to definitely create some interest around the state, because it's such a big land lot and a large, beautiful freehold building."

"There is interest from all around the state, from Sydney and other regional operators, in any pub in a strong area, and Wagga is a strong area."

The Riverina Hotel, bistro and bottle shop, about 450 metres north of Romano's, was sold off-market in November reportedly for more than $5 million.

Brokers HTL Property's Blake Edwards and Sam Handy are handling the sale, which they say will attract interest from regional and Sydney buyers.

Given the property's B3 commercial core zoning, 2189sqm land holding and 16-metre height approval, development potential is an "obvious" upside to the listing.

"We anticipate that there will be a mixture of local interest, buyers from some of the larger surrounding regional centres and most definitely from Sydney," Mr Handy said.

"Unequivocally, there won't be another regional pub with these core trading attributes and this level of upside coming the the market in the foreseeable future."

Romano's regular customer Ros Prangnell, from Wagga, said she hoped any new owners would continue to run a pub in the building as it was a good meeting spot for community groups.

"I'm not a drinker, I don't drink alcohol but I see the pubs as a pretty important venue from a community point of view," she said.

"At Romano's, you've got the Murrumbidgee Rotary Club meeting there, as well as the Amnesty International and I've seen others. It's pretty important to be able to meet and have a meal."

Mr Handy said his "phone has been running hot" with inquiries "mainly from pub operators and some hotel operators who were interested in the accommodation rooms".

Mr Handy said the site's B3 commercial core zoning could attract other types of development.

Mr Barnhill said he did not know if any Wagga buyers might bid for Romano's but there were "similar operators around town".

Romano's operates with 15 gaming machines attached to the licence, which allows it to trade to 3am.

It features a bar, bistro, gaming room, beer garden, alfresco streetside dining and first floor function rooms with their own kitchen.

The first and second floors contain 45 accommodation rooms that are unused by the current owners.

Regional pubs are experiencing a boom as buyers turn to quality in the bush as well as that in metropolitan and coastal areas, Mr Edwards said.

"With well above average transactional volumes across both metropolitan and coastal hotels over the last 24 months, the availability of quality stock is rapidly diminishing with operators now seeking quality regional assets," he said.