A court has dismissed an appeal over planning permission that was granted for a £240m waste incinerator.
Planning permission for the facility was approved by a Department for Infrastructure civil servant in 2017.
That decision was overturned when the High Court held that the incinerator had been unlawfully authorised.
The landmark ruling could have wide-ranging implications across Stormont departments.
Arc21, the organisation behind the facility, said it was "disappointed" at the latest decision.
A spokesman for the Department for Infrastructure said it was "carefully considering today's judgement".
The Court of Appeal judges ruled that the waste facility was "controversial" and "significant".
"It would be contrary to the letter and spirit of the (Good Friday) Agreement and the 1998 (Northern Ireland) Act for such decisions to be made by departments in the absence of a minister," they said.
The court also said the decision was a "cross-cutting decision" that involved several departments.
"This is no support in the (Good Friday) Agreement for the suggestion that cross-cutting matters can be dealt with by departments in the absence of ministers."
A spokesperson for Arc21 said: "This is a disappointing ruling that Arc21 and its stakeholders will now review."
'Dead in its tracks'
David Fry, assistant director of the Construction Employers Federation said the judgement had "huge implications for a number of major infrastructure projects that were either due to proceed imminently or are in the planning process".
If I look at that from the perspective of how the public sector construction pipeline is brought forward and delivered, then that's not far off stopping it dead in its tracks @JP_Biz— David Fry (@DavidFry1984) July 6, 2018
The Becon Consortium, the private sector bidder hoping to build and run the Arc21 project, shared their disappointment at the judgement.
"We note however that today's ruling does not in any way change the material facts or merits at the heart of the planning decision itself, the project's compliance with regional waste policy or indeed remove the strategic need for such infrastructure here in Northern Ireland in the future.
"Instead, the court's decision is entirely based on procedural matters surrounding the ability of the department to make a decision in the absence of a minister in post."
Colin Buick, chairperson of NoArc21, an opposition group, said they were "delighted" with the decision.
"We successfully argued that in the absence of a Northern Ireland Executive Department for Infrastructure (DFI) minister, or replacement Northern Ireland Office direct rule minister, that the Permanent Secretary at DFI did not have lawful authority to issue the planning approval," he added.
"We hope that today's judgement will act as a wake-up call to DFI.
"Now is an opportune time for the department to take stock and completely review its waste management strategy."
Sinn Féin MLA Declan Kearney welcomed the ruling saying it was "another vindication and another victory for local democracy, campaigning residents and the primacy of the Good Friday Agreement".
"Approval should never have been granted for this facility in the first place given the widespread opposition and concerns over the safety of residents," Mr Kearney said.
Mr Kearney added: "The Court was very clear that it would be contrary to the Good Friday Agreement for such a significant and controversial decision to be taken by departmental officials in the absence of an Executive.
"I very much welcome that as it again signals the importance of re-establishing the power-sharing institutions in a way that is consistent with the Good Friday Agreement."
However the DUP leader and former first minister Arlene Foster said the "judgement brings a sharp focus on the impact in Northern Ireland of no local Ministerial decision-making" and cannot be allowed to continue.
"In the absence of an Executive, decisions must be made in London," Mrs Foster said.
SDLP deputy leader Nichola Mallon said "clear perimeters" have now been set around the ability of senior civil servants to make decisions.
"It's clear from this ruling that if it's controversial, if it's cost-cutting and if it's significant, then it doesn't fall within the authority of the civil service to make... that throws up huge political questions," said Ms Mallon.
Former Alliance Party leader David Ford said the Arc21 judgement has shown a need for Secretary of State Karen Bradley to address how vital issues are dealt with in Northern Ireland.
In the absence of an executive, he believes the pressure is now on the secretary of state.
'A back seat driver'
Ulster Unionist Party leader, Robin Swann, said the decision means that Secretary of State Karen Bradley "has now run out of road".
"She can no longer remain a back seat driver and must move to restore some form of devolution or the government should appoint direct rule ministers on Monday.
"The Secretary of State and the Northern Ireland Office can no longer duck the hard decisions for fear of upsetting Sinn Fein or concerns about the DUP's confidence and supply agreement with the Conservative Party."
A UK Government spokesperson said it had noted the court's decision, "and will consider the judgment carefully".