Spurs sit third from bottom, two points from safety, with just five matches remaining. Their 2-2 draw against Brighton last weekend - where they conceded a stoppage-time equaliser - has extended their winless league run to 15 games and deepened concerns around the club.
They now travel to Molineux Stadium on Saturday to face Wolverhampton Wanderers, knowing victory could lift them out of the relegation zone if results elsewhere go their way, particularly involving West Ham United and Everton.
De Zerbi has made it clear that handling pressure will define their survival hopes.
"We are suffering, they are suffering because it is not easy to play in this condition," he said. "But they have to be stronger."
The Italian added that focus must remain fixed on securing a result.
"We have to live every part of the day waiting for a win and preparing for a win. With a win we can change this moment."
Injuries continue to disrupt Spurs' preparations. Destiny Udogie is ruled out with a muscle problem, while Guglielmo Vicario remains unavailable after hernia surgery, meaning Antonin Kinsky is set to start in goal again. James Maddison travels with the squad but is not expected to feature despite returning to the bench last time out.
De Zerbi, appointed after spells for Thomas Frank and Igor Tudor earlier this season, recognises the challenge posed by a Wolves side playing without pressure.
"It's a tough game because they have nothing to lose," he said. "We have to be able to play without too much pressure."
Despite growing criticism, De Zerbi has backed his players' attitude.
"I found good players, serious players. They follow me and believe in my words," he said.
For Tottenham, the equation is now simple - handle the pressure and win, or risk slipping closer to relegation.