As if overcoming a 3-1 deficit was not bad enough, Spurs have had to travel to Portugal without 11 first-teamers for the last-16 return leg.
Hugo Lloris, Erik Lamela, Etienne Capoue, Mousa Dembele, Paulinho and Emmanuel Adebayor are all sidelined for the clash in Lisbon, where the north Londoners' defence is the biggest concern.
Michael Dawson, Vlad Chiriches, Younes Kaboul and Kyle Walker are all out injured, while Jan Vertonghen's suspension has only compounded matters.
Such paucity of options means Sherwood has had to bring seven players who have yet to play for the first team to Portugal for a match he hopes to restore some pride in.
"It would be massive to win this - there would be no bigger than this one," he said. "We've got an uphill task and we know that.
"We know it will be very, very tough, but we are professional people and we have to come with optimism and hopefully we can do the club proud again tomorrow night.
"I won't throw any of them on unless I need to. There's a time and a place to blood young talent.
"Unless we absolutely need to they won't be thrown into this lion's den because you could end up killing someone's career before it's even started.
"Some of these boys are apprentices. These boys are young kids, nowhere near ready to play in Tottenham's first team.
"It is needs must. They are next in line to play. We've got a crippling injury list back at home. It really is severe and we're having to bring these boys."
The youngsters that have travelled to Lisbon vary from 16-year-old attacking midfielder Joshua Onomah to Scotland Under-21s goalkeeper Jordan Archer, who is likely to be back-up to Brad Friedel at the Estadio da Luz.
The 42-year-old will not be the only experienced head in the Spurs starting line-up, but the worrying lack of options from the bench means a fourth successive loss is a distinct possibility.
Another defeat would heap further pressure on Sherwood, who had to answer yet more questions about his future at the pre-match press conference.
Louis van Gaal is the bookmakers' favourite to take the White Hart Lane helm and he recently fuelled speculation by reaffirming his desire to manage in the Premier League.
However, Sherwood, who was given in an 18-month deal when succeeding Andre Villas-Boas in December, was unmoved by the Netherlands manager's latest comments.
"People ask me this all the time, he is obviously destined to want to manage in England," Sherwood said.
"He has got a good track record, he is a good manager and I'm sure he'll get his opportunity: he's been shouting loud enough for it."
Van Gaal is not the only manager to irritate Sherwood, who is preparing for the second part of his clash with Benfica counterpart Jorge Jesus.
Having quarrelled throughout last week's match, the Portuguese showed the Spurs boss three fingers after Luisao made it 3-1.
Sherwood was quick to reject suggestions Jesus mentioned Villas-Boas when goading him, but clearly has little time for the Benfica manager and joked he might give him a hand gesture of his own on Thursday.
Asked if he would like to celebrate by showing five fingers, he said with a laugh: "It would be nice. Or one.
"I took it as disrespectful but we move on. I've got a lot of respect for this great club, Benfica. As far as I am concerned, it is case closed."