The Border region counties of Cavan, Donegal, Leitrim, Monaghan and Sligo are at risk of economic decline despite growth in the broader economy.
The latest IrishJobs.ie index shows there has been a 7% year-on-year increase in vacancies nationally.
Despite this, many counties in the border region are experiencing declines - with Cavan and Leitrim the worst affected with job vacancies dropping by 27% and 17% year-on-year respectively.
Counties Cavan, Donegal and Monaghan have the lowest job vacancy rates in the country.
A lack of infrastructure is stunting growth, according to the website.
"Continued failure to address under-development in the Border region could trigger a cascade effect, whereby businesses and professionals take flight to more lucrative parts of the country—essentially a ‘brain drain’," said Orla Moran, General Manager of IrishJobs.ie.
"This would cause long-term damage to the region that would be difficult to reverse.
The continued uncertainty surrounding Brexit and what it will mean for the border region is also having an impact.
"The same problems apparent in the immediate aftermath of the 2016 EU referendum are still apparent in 2018," said Ms Moran.
"Ireland’s decade-long journey from deep recession to rapid growth is a testament to the benefits of an open economy and a business-friendly government.
"To maintain this upwards trajectory, and guard against major risks like Brexit, industry and policymakers must work to repair the chinks in Ireland’s armour, namely by ensuring we meet the skills requirements of a modern economy, and by providing the structural prerequisites for enterprise and job creation in regions outside the capital."