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Spurs found themselves leading 3-1 with 15 minutes remaining but Southampton secured a stunning late comeback with goals from Theo Walcott and a stoppage-time penalty from James Ward-Prowse.
The result sees Spurs remain in fourth place in the table but have played two games more than Newcastle United and Liverpool.
Speaking in his postmatch news conference, Antonio Conte appeared to aim a dig at the club's ownership.
"They're used to it here. Don't play for something important. They don't want to play under pressure. They don't want to play under stress.
"Tottenham's story is this. Twenty years there is the owner and they never won something. Why? The fault is only for the club, or for every manager that stay here. I have seen the managers that Tottenham had on the bench.
"It is time to change this situation if Tottenham want to change. If they want to continue in this way, they can change the manager, a lot of managers, but the situation cannot change. Believe me."
Spurs also face an important injury concern after a tearful Richarlison had to be withdrawn inside the opening five minutes.
Conte's side face Everton after the international break on April 5.