Tony Blair will warn this week that Britain's future prosperity relies on the country remaining a committed member of a strong European Union.
Amid mounting Tory calls for the UK to draw back from the EU, or even leave altogether, the former prime minister will urge the Government to remain fully engaged at the "top table" of European politics.
The coalition is committed to renegotiating Britain's relationship with Brussels and winning back powers, while a smaller core of EU members of the euro move towards closer union.
The eurozone debt crisis has given new impetus in recent years to demands from many Conservatives for an in/out referendum on UK membership of the EU.
But, in a speech in London on Wednesday, Blair will warn against incremental changes and call instead for a "grand plan" that does not imperil Britain's economic prosperity.
An aide said: "He will outline why Britain needs to be at top table and why in all the detailed negotiations it's important to not lose sight of the economic benefits that being part of a strong EU brings."
Blair will stress that 47% of British exports go to other members and that 50% of foreign direct investment to the UK is from the EU.
Brussels talks on the next seven-year EU budget broke up on Friday without a deal, with Cameron warning that Europe has to live in the "real world".
Former Labour foreign secretary David Miliband said that other EU members are frustrated and angry with Britain because it does not take Europe seriously enough.
He told BBC1's Andrew Marr Show it is a "tragedy" that it has taken the coalition Government two years to discover it has "allies in Europe" after Germany, Sweden and Denmark came out in support of the UK in budget negotiations last week.
"Britain is better off in Europe and, critically, Europe is stronger with Britain in it," he told BBC1's Andrew Marr Show.
"I cannot over-emphasise the sense of disappointment, frustration and anger that exists on the continent at not only us betraying our own future but betraying their future by not being part of the European debate in a very, very serious way.
"It's got big consequences for Britain. No serious power in the 21st century is going to be divorced from its neighbours. It's just a matter of fact."
But Tory eurosceptics stepped up their demands for an in/out referendum on the EU.
The Prime Minister has signalled his readiness to hold a referendum but only on the new settlement between Westminster and Brussels that he intends to achieve over the coming years.
Influential backbencher Mark Pritchard, a former secretary of the 1922 Committee of Tory MPs, urged ministers to bring forward legislation for a referendum before the end of the parliament.
"This should be an in/out referendum - anything short of that simply won't deliver," he said in an article for the Telegraph website.
Foreign Secretary William Hague reiterated that there would be a referendum to seek "fresh consent" from the British people in the wake of renegotiation and the eurozone crisis.
"We do believe that sometimes less is more in Europe, that doing less at the European level is better for this country and for other countries.
"And what we've said is that when we see how that crisis in the eurozone plays out and when we've tried to improve our relationship with Europe, well that will be the time to seek fresh consent from the British people and the cleanest and clearest way of doing that would be in a referendum," he told Marr.
"But we will spell out our policy for the coming years and for the next general election when the Prime Minister speaks about these things."