The 27-year-old Spaniard again needs an operation on the anterior cruciate ligament in his right knee, as well as the medial collateral ligament, after pulling up in training last weekend.
And as Wolves get ready to face Fulham at Craven Cottage, Nuno confirmed the fans' favourite – going under the knife for the second time in less than a year – will begin his road to recovery soon, with the club currently analysing which type of surgery is most suitable for him.
"I would expect next week to be the right moment to do it," said the Wolves boss.
"But all that part is with the doctors. The decision is being really responsible and taken care of.
"We need to make sure Jonny is strong, confident and has no doubts in his head. We have to make sure that he is confident, with absolute trust he is going to return."
Otto's latest injury came as a bitter blow, having not long been back from six months on the sidelines.
He returned to action in February, after suffering his first injury in the Europa League against Olympiacos last August, and had played seven Premier League games.
On whether the latest issue came as a result of a tackle during training, Nuno said: "No, no. It was very similar to what happened with the first one.
"When he put his right foot on the ground, he was unbalanced and he felt something.
"I don't think even he could explain exactly what, but he felt it.
"After the assessment of the doctor was the worst news we could get."
There is no definitive time frame on Otto's injury at this early stage, but Nuno is confident he will come back stronger.
Asked if they know why the injury reoccurred: Nuno said: "Yes, but I think I'm not the right person to say it.
"It was a meeting between us and the medical department, analysing the situation and why. But it wouldn't be fair to do it in public.
"I'm sure (he will play again), because the doctors, Jonny, myself – we all know why.
"That's why we are so worried about finding the right surgery for him to do, so he doesn't have any setbacks on the same situation.
"That's more important now, to decide well and assess the surgery he's going to have to face."
Wolves, meanwhile, 'have to decide' whether Joao Moutinho can feature against Scott Parker's side.
The Portuguese missed the 3-2 defeat against West Ham on Monday night with a groin issue – sustained while on international duty last month.
Willy Boly, who is currently self-isolating with Covid-19, will miss out, though, along with long-term absentees Raul Jimenez and Fernando Marcal.
"Let's see with Joao. We still have to decide whether he will be in the squad or not. He's not 100 per cent," added Nuno.
"Boly is allowed to join us, I think, on Tuesday. That's when the isolation period finishes.
"Raul is training like the previous weeks. He's with the team, but we still have to wait for the clearance from the doctors.
"It's still the same with Marcal. He's still a little bit far from joining the group."