Meanwhile, the Ligue 1 outfit make the trip to St Mary's having lost just one of their six fixtures ahead of the new Ligue 1 campaign.
Match preview
On the back of last season's 15th-placed finish in the Premier League, Southampton supporters understandably had their concerns about how their club could fare in the summer transfer window.
However, as well as retaining the services of key man James Ward-Prowse, the Saints have made some notable additions as Ralph Hasenhuttl attempts to move his team back up towards the mid-table positions.
The signing of Rangers playmaker Joe Aribo stands out, but Southampton have every reason to be optimistic about the acquisitions of Gavin Bazunu and Romeo Lavia from Manchester City.
As it stands, though, the changes in personnel have not led to an improvement on the pitch, Southampton still looking for their first win of the summer.
Since a 3-1 defeat against RB Leipzig, goalless draws have been posted against Austria Klagenfurt and Watford respectively.
From Monaco's perspective, head coach Philippe Clement has had to watch Aurelien Tchoumanei depart the club to sign for Real Madrid.
That said, there is every reason for Clement and the club's fans to be optimistic as they look to cement a place in the top three of Ligue 1 and attempt to qualify for the Champions League group stages.
As well as signing Takumi Minamino and Breel Embolo, Monaco went through their first five pre-season games unbeaten, the last of that run being a 2-2 draw with Inter Milan.
Although they went down 2-1 to Porto in Portugal on Sunday, Clement will be satisfied with the competitive work-out for his players ahead of making the trip to England.
Southampton Club Friendlies 1 form:
Monaco Club Friendlies 1 form:
Team News
Hasenhuttl was able to name just six substitutes for the fixture against Watford on Saturday, and those who missed out on the starting lineup may come into the team for this game.
Lyanco could replace either Jan Bednarek or Mohammed Salisu, while Oriol Romeu and Ibrahima Diallo may get the nod in the centre of midfield.
Che Adams stands to feature in attack, but Hasenhuttl will have to consider how to handle the wing-back areas with Kyle Walker-Peters and Moussa Djenepo both playing the full game at Vicarage Road.
Clement will likely decide to restrict anyone who played 90 minutes against Porto to an appearance off the substitutes' bench for this game.
That would see Alexander Nubel, Axel Disasi, Caio Henrique, Jean Lucas, Eliot Matazo, Kevin Volland and Wissam Ben Yedder all drop out of the side.
Southampton possible starting lineup:
Bazunu; Bella-Kotchap, Bednarek, Lyanco; Armstrong, Romeu, Diallo, Djenepo; Aribo, Elyounoussi; Adams
Monaco possible starting lineup:
Didillon; Vanderson, Couto, Maripan, Jakobs; Minamino, Fofana, Coulibaly, Gelson Martins; Musaba, Embolo
We say: Southampton 1-1 Monaco
With Monaco having performed better during pre-season and possessing more games under their belt, they are the favourites to prevail on Wednesday. Nevertheless, Southampton will welcome the chance to impress against a bigger club, leading us to predict a competitive draw.