Rodrigo Bentancur handed Spurs an early lead in the fifth minute, but Villa fought back through Morgan Rogers, who ended a 20-match goal drought with a stunning strike in the 37th minute. Emiliano Buendia then came off the bench to curl home a superb winner in the 77th minute, sealing Villa's fifth consecutive league victory.
The defeat means Tottenham have suffered 11 losses and managed just three wins in their last 18 Premier League games at the Tottenham Hotspur Stadium, a run that has continued under Frank, who joined from Brentford in the summer.
Asked to explain the team's alarming home record, Frank admitted there was no simple answer.
"I hope I can. Maybe, I don't think it's that simple," the Dane said. "I think it's about looking into the performances. that's probably the reason I think it's a game that is a draw, a clear draw and we could easily have won it instead of Villa and then it would have been a different narrative.
"So, I look at the performance on the pitch, we did well, and look at the bits we need to improve."
Tottenham's injury concerns deepened before kick-off as captain Cristian Romero pulled out of the warm-up with a minor adductor issue, while Mathys Tel was forced off in the 60th minute due to a calf problem and was seen with an ice pack on the affected area. Both players are now set to join the club's growing injury list.
Despite the setback, Frank defended his team's performance. "I think we performed quite well. What is, maybe not through the roof," he said. "Vicario didn't have to make a save. So we've done that and then you've done well.
"We gave two goals away. if you said to me before the game, they will shoot from there, Rogers and Buendia. I said, yeah, of course, no problem, it's not dangerous. But a fantastic quality shot from Rogers."
Villa's victory not only halted Tottenham's seven-match unbeaten run in all competitions but also highlighted the scale of the challenge Frank faces in turning their home form around ahead of next weekend's trip to Everton.
Nottingham Forest are set to receive a double injury boost ahead of their Premier League showdown with champions Liverpool after the international break, with both Chris Wood and Callum Hudson-Odoi expected to return to action.
David Moyes has praised James Garner for his outstanding form this season, saying the Everton midfielder is edging closer to an England call-up.
Leeds United manager Daniel Farke has provided a detailed update on the club's injury situation as the Whites head into the international break aiming to reset after a frustrating run of results.
Arne Slot believes Liverpool's toughest spell of the season is now behind them, with a crucial run of winnable fixtures offering a chance to reignite their campaign after a heavy defeat to Manchester City.
