Villas-Boas suffered the biggest home defeat of his reign as the Hammers ran riot, claiming victory thanks to three goals in 13 second-half minutes.
Spurs had only conceded two goals prior to the game but Andros Townsend looked the only player capable of making a difference for the north London club, and the fans who were left inside White Hart Lane at the final whistle made their feelings known by booing the team off the pitch.
Villas-Boas, who had claimed four wins from six games prior to the derby, called for a bit of perspective, though.
"It's a wake-up call that we have to react to, we have to bounce back and I trust the team to do that," the Spurs boss said.
"I think we can't undermine what we have been doing up to now.
"Obviously it's a defeat. Had we won this game we would have been just one point behind.
"It's something we don't like, but we have to put into perspective of what we've done before."