The Hornets have won five matches in a row and occupy second place heading into the final stretch of the season, while Wednesday are in the relegation places.
Xisco's side have won nine of their last 10 matches and are six points better off than third-placed Swansea City, who have a game in hand to play.
Watford's promotion fate is very much in their own hands, then, but six of their remaining eight fixtures are against teams in the top 10, including Swansea on the final day.
Xisco deserves huge praise for guiding Watford up the table since his first game in charge on Boxing Day, with no side taking more points than the Hornets' 41 since then.
Not since January 2011, when Malky Mackay was in charge, have Watford won six league games in a row, but that is something they will be confident of achieving on Friday.
However, despite Wednesday's lowly position, they did pull off a shock 2-1 win away at Yorkshire rivals Barnsley just before the two-week hiatus.
The Owls are now unbeaten in two, having also played out a 1-1 draw with Huddersfield Town, and are six points adrift of 21st-placed Birmingham City with a game in hand.
Moore's men quite simply need to put a winning run together if they are to bridge that gap, but they are winless in their last four league games against Watford since 2013.
This will be Wednesday's first trip to Vicarage Road in the league since May 2015 when playing out a 1-1 draw on the final day of the Championship season.
Captain Troy Deeney is moving closer to a return to action, having missed close to two months, but this game will come too soon for the striker.
Fellow attacker Sema is a major doubt, meanwhile, as he started Sweden's World Cup qualifier against Estonia on Wednesday.
As for Wednesday, they are expected to be without a number of first-team players for this trip to Vicarage Road.
Keiren Westwood was forced to pull out of the side that beat Barnsley due to an injury in the warm-up, but he should be back involved here.
Striker Rhodes seems certain to lead the line after scoring three goals in his last three Championship games, which is as many as in his previous 33.
Watford possible starting lineup:
Bachmann; Femenia, Troost-Ekong, Sierralta, Masina; Chalobah, Hughes, Gosling; Pedro, Success, Gray
Sheffield Wednesday possible starting lineup:
Westwood; Urhoghide, Lees, Borner; Palmer, Pelupessy, Bannan, Reach; Paterson, Windass; Rhodes
We say: Watford 2-0 Sheffield Wednesday
Wednesday revived their survival hopes before the international break with an impressive win at high-flying Barnsley, but they face a Watford side in superb form.
The Hornets have won five in a row, and nine of their last 10, so we cannot see past a home victory in this Good Friday fixture.