An artist's impression of the proposed 50,000-seat stadium
Everton's ambition of moving to a new home in Kirkby appears to be over after the government rejected a planned £400m stadium and retail development.
Communities secretary John Denham confirmed his decision on Thursday.
He raised concerns over the possible harmful effects on the "vitality and viability" of local communities.
Everton chief executive Robert Elstone said the club will review the rejection before deciding their next step but that the news was "very disappointing".
The decision can be challenged by a letter to the High Court within the next six weeks.
The verdict could hit Liverpool's hopes of being part of England's bid to host the 2018 World Cup finals, the decision on host cities to be made on 16 December.
The development would have seen Everton move from Goodison Park in Liverpool to the 50,000-seat stadium in Kirkby as part of a complex with a Tesco superstore and other shops.
But, following a public inquiry earlier this year, Denham has decided that the move would breach shopping policy which discourages major supermarket chains from taking business away from town and city centres.
[A ground share is] not on our agenda at the moment
Liverpool deputy executive director Peter Shaw
The move was expected to bring up to 7,000 jobs to the town, which is a suburb of Knowsley, and local MP George Howarth said: "I regret this decision in a time of significant economic challenge to Merseyside."
News of the plan's rejection was welcomed by Dave Kelly, the chairman of the supporters' group Keep Everton in our City (KEIOC).
"[KEIOC] repeatedly questioned the cost of the stadium, the chosen location flew in the face of perceived wisdom, overall this project represented an unacceptable risk to Everton Football Club," said Kelly.
"[The] decision should be looked on as a positive, we have been saved from the road to continued mediocrity.
"After a period of calm reflection we hope Everton have had the foresight to develop a contingency plan that all fans can embrace."
Everton chief executive Elstone told BBC Radio 5 live that he would be speaking to Knowsley Council and Tesco before deciding on future plans.
"In the short term we need to review the decision and the reason for the rejection," said Elstone.
"We'll do that with our commercial partners, with Tesco and Knowsley, and determine how we move forward.
"Before that we won't know precisely what our next step will be... a determination to drag this club forward is part of our fabric.
"All the hard work over a long period of time has been motivated by one thing, to take the club forward.
"[We want to] put the club on a firmer financial footing and, ultimately, give [manager] David Moyes a fairer crack of the whip in the transfer market.
"We've punched well above our weight for a number of years... I don't think a smaller stadium [plan] would work for Everton Football Club."
Elstone did not rule out the possibility of a ground-share with rivals Liverpool, whose plans to build a new £350m stadium in Stanley Park have been hit by delays.
Everton decision affects city bid prospects - Elstone
"It's certainly one of the options that we will need to cover," said Elstone. "A shared stadium is perhaps an option if it's affordable."
But Liverpool deputy executive director Peter Shaw said: "[A ground share is] not on our agenda at the moment. Liverpool are progressing forward with our own stadium. That is the position we are still in."
Ian Morris, of the Kirkby Residents' Action Group, who opposed Everton's planned move, said of the rejection: "That is brilliant, it is fantastic news.
"The club have a major problem with no new stadium and will have to look at redeveloping Goodison.
"But our campaign was never about football, it was about the town we live in.
"We believe the football stadium would have destroyed our town.
Everton have endured a challenging season on the pitch
"Kirkby is only a small town and they were talking about a 55,000-seater stadium built right in the town with a huge retail development which we thought was inappropriate.
"It would have had a major negative effect on the retailers working in the existing town centre.
"The stadium would have disrupted everybody's lives every time there was a football match."
Everton, who had already lost one planning battle when hopes of raising £10m through the redevelopment of the club's training ground for housing were dashed in January, were set to contribute £78m to the scheme.
The off-field disappointment compounds on-field woes, with Wednesday's 3-2 loss at Hull being Everton's sixth Premier League defeat of the season.
Manager David Moyes berated his team for a lack of fight, the Toffees now having won just one of their last 10 games in all competitions since the start of October.
"We could be dragged into a relegation fight - particularly because of the injuries and individual performances," said Moyes, who had to contend with half-a-dozen first-teamers out injured against Hull.
"But I am the one who has to take responsibility for the team. I pick the team and I sign them. I'm the one who has the ultimate responsibility."
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