The Blades currently sit 18 points adrift of the drop zone with only 21 points left available, meaning that this weekend depending on other results, they could mathematically make the drop back down to the Championship.
Compared to recent seasons, this campaign has been relatively disappointing for Nuno's men as with them being placed in 12th position with only seven games remaining, qualification for the Europa League next season is out of the question.
It has been a season that has been marred by injuries and there is no doubt that has halted their progress with star man Pedro Neto being the next to be added to the long term injury list.
This was after he suffered a knee injury at Craven Cottage leaving him out for the rest of the season.
The winger joins the likes of Raul Jimenez and Jonny Otto and the lengths of the injuries to some of the Wolves players will certainly be something that will have frustrated Santo this season.
With these absentees, it could give an opportunity for Vitinha to step up to the plate in the number 10 role and make a bit of a statement to prove why Wolves should buy him on a permanent deal when his loan deal is up at the end of the season.
In positive team news for the Wanderers, midfielder Joao Moutinho made a return last time out meaning he could be involved from the start against the Blades and Willy Boly could also feature after recovering from his period of self-isolation.
In terms of the system the hosts will play, after opting to go with a four at the back in the win at Fulham and it proving to work, it would be very surprising to see if he changed from this and reverted to a three at the back.
The other interesting decision that Santo will have to make is to choose to whether to start Willian Jose or Fabio Silva as the youngster has impressed in recent weeks and had a big hand in last weekend's winner.
Due to this, many would argue that he deserves a spot in tomorrow's starting eleven compared to Jose, who it is fair to say has not made much of an impact since being brought in on loan back in January.
Patricio, Semedo, Saiss, Coady, Ait-Nouri, Moutinho, Dendoncker, Vitinha,Podence, Traore, Jose
It has been a nightmare of a season for the Blades as they have only managed to accumulate four wins and pick up 14 points.
After Chris Wilder departed the club last month, the club remains managerless with Paul Heckingbottom in interim charge and relegation is a matter of when, not if.
Similar to Wolves, their squad has been filled with injury problems and another one was added this week when it was announced that both Billy Sharp and Oli McBurnie will be unable to feature for the rest of the season.
They join an injury list that features Chris Basham, Jack O'Connell, Jack Robinson and Sander Berge.
In good news for Heckingbottom's side, Jayden Bogle and George Baldock could start after being included in the matchday squad last time out against Arsenal after both suffering from a suspected concussion against Leeds United at the start of the month.
Ramsdale; Ampadu, Egan, Stevens; Baldock, Lundstram, Norwood, Fleck, Osborn; McGoldrick, Brewster
Despite it not being a great season for the Wanderers, if they do not earn anything but three points here it must be considered a bad result considering the terrible campaign that their opponents have had.
This is even without the presence of arguably the best player of the season, Neto. There is no doubt that Daniel Podence has the quality to fill in his role and be a threat down that left-hand side.
The important thing for the hosts will be to ensure that the service into either Jose or Silva is good or it could be a long frustrating night for Nuno's side.