Heavyweights England and Uruguay must resurrect their World Cup hopes or face the prospect of an early flight home when they collide in a crunch Group D fixture on Thursday.
Opening defeats to Italy and Costa Rica respectively have left both countries in danger of elimination with little room for error in their last two pool games.
Defeat in Sao Paulo would surely spell doom for either Roy Hodgson's new-look England or two-time winners Uruguay, who were unimpressive in their 3-1 loss to Costa Rica.
Combination photo shows Uruguay's defender and captain Diego Lugano (L) and England's midfielder and captain Steven Gerrard.
Both countries have question marks over their strikers with calls in British media to either drop talisman Wayne Rooney, or move him from the left to his preferred central role.
For Uruguay, Liverpool's Luis Suarez, this season's Premier League top-scorer with 31 goals, is set to make his return from keyhole surgery on his the meniscus in his left knee last month.
Rooney set up England's goal but missed a chance to equalise during Saturday's 2-1 loss to Italy, in a subdued display which had many critics questioning his place.
The Manchester United forward, 28, is still to score at a World Cup and when he was spotted training with the reserves on Monday, speculation rose that he had been axed.
But the English FA said Rooney had requested an extra training session while other first-team regulars continued their post-match recovery.
Rooney complained "sometimes (I) wonder what the press are getting at" on his Facebook page, while Frank Lampard hit out at the obsession with his team-mate.
"A fixation with one player can become, rather than a debate, a bit of an agenda," he said. "So I do think we need to drop the agenda and look at the team, whoever plays."
The whirlwind surrounding Rooney has dominated the build-up for youthful England, who won praise for their bold approach against Italy, exemplified by Raheem Sterling.
However, defensive fragility could return to haunt them with problems down the left, while centre-half Gary Cahill was out-jumped by Mario Balotelli when heading the winner.
Uruguay have their own worries at the back after their defence was repeatedly rattled by Costa Rican strikers Joel Campbell, who is on Arsenal's books, and PSV Eindhoven's Bryan Ruiz.
They will also be missing Benfica defender Maxi Pereira, who was sent off for a foul on Campbell in the tail-end of Saturday's game.
But England will be wary of a strikeforce pairing Paris Saint-Germain's Edinson Cavani with the lethal Suarez, even if he won't be fully match-fit.
The build-up has not been short of hyperbole with Uruguay coach Oscar Tabarez calling it a "final" and captain Diego Lugano describing it as "life and death".
England's Daniel Sturridge, who was on target with a sweet first-time finish against Italy, said it would be "do or die" in Sao Paulo.
"I'm prepared to do anything, and I'm talking anything. I'm being serious. It's do or die," he told reporters.
The rivalry dates back to May 1953, when goals from Julio Cesar Abbadie and Omar Oscar Miguez saw off England 2-1 in Montevideo. Uruguay lead the head-to-head 4-3, with three draws.
In their only World Cup meetings, holders Uruguay won 4-2 in the 1954 quarter-finals and they drew 0-0 in the group stage in 1966, when England won their only World Cup title.
The latest instalment will be refereed by Spain's Carlos Velasco Carballo, who is taking charge of his first World Cup finals game.
Both teams will keep a close eye on the other Group D result between Italy and Costa Rica, 2,000km (1,200 miles) away in Recife on Friday.