Spurs progressed to a fourth-round tie at Burnley after winning 3-2 on penalties following a 2-2 draw after 90 minutes at Molineux.
Ndombele opened the scoring with a fine run and finish and completed 90 minutes for the first time this season but was at fault for both the hosts’ goals.
He was first beaten in the air by Leander Dendoncker and then lost possession in midfield ahead of Daniel Podence’s second-half equaliser.
Harry Kane had put Spurs 2-0 up in the first half but the match was decided on spot-kicks, with Ruben Neves, Dendoncker and Conor Coady all missing as Bryan Gil’s goal proved decisive.
Asked about Ndombele afterwards, Nuno said he did not want to discuss individuals but admitted the Frenchman needs time to get up to speed.
Ndombele did not feature in pre-season or in the first four League games of the season after asking to leave the club over the summer.
“Let's try to avoid as much as we can individual analysis,” Nuno said. “We will do it and we will do it amongst ourselves. I think we have to be patient with Tanguy because all that happened in pre-season and this is his third game and already we've had however many games we've played so far.
“So let's be patient with all our players and patient with the time that they need to get to the level that I truly believe their talent can allow.”
Nuno was frustrated that Spurs conceded from a set-piece for the second game running after falling behind to Thiago Silva’s header in Sunday’s 3-0 defeat to Chelsea.
The visitors were causing problems before Dendoncker beat Ndombele to a deep corner and headed past Pierluigi Gollini to swing the momentum back to Wolves.
“I’m disappointed with the set-piece,” Nuno said. “We cannot allow it because the momentum changes, the atmosphere changes and in the second half it wasn't as we wanted which like you say the first half was really good.
“I think we started the second half well, we had chances but then the atmosphere of Molineux is hard. They got the draw and then we've been able to control the moment until the end.”
Gollini saved from Dendoncker, while Neves and Coady both missed the target in the shootout, and Nuno insisted the victory was not down to luck.
“The boys prepared well yesterday and we spent a lot of time preparing because it's not luck,” Nuno added. “It's having a goalkeeper who has the right info and it's having the players making their responsibility and the tasks that they have to do it. I think I said a lot about the game today.”