Spurs' difficult start to the season continued on Tuesday night when they lost on penalties to Colchester United in the EFL Cup, while the Saints recorded a 4-0 win over local rivals Portsmouth in the same competition.
Mauricio Pochettino's side have struggled thus far this season for consistency and results, with their draw in Greece against Olympiacos and defeat to Leicester City, both games in which Spurs took the lead, highlighting their problems.
Defensively the North London club have lacked the organisation and structure that has been a staple of the Pochettino era, while going forward they have often been profligate, as was the case against Colchester in midweek.
Although Spurs have endured slow starts before under the Argentine, this season's struggles have increased speculation that the former Saints boss could be leaving Tottenham relatively soon for pastures new in either Manchester or Madrid.
While those rumours of rifts in the squad and players having 'different agendas' could continue to affect their performances, it is likely that this game will yield a positive response from Pochettino's players, with the Argentinian likely to make a few changes.
One such change will be to bring back striker Harry Kane, who has scored nine in nine games for club and country already this season, after he missed the game in the EFL Cup.
Worryingly for the Saints, the England star has a tremendous record against them, scoring eight in his previous nine appearances in this fixture.
Erik Lamela is also likely to be brought back into the side after featuring in all their previous league games, while goalkeeper Hugo Lloris is expected to return after missing the Leicester fixture to be with his wife for the birth of their new child.
Lloris's leadership, experience and cool head at the back will be essential as Spurs look to regroup and deliver a solid performance against a side who will be comfortable to sit back and hit them on the counter with the pace of Nathan Redmond and Che Adams.
Interestingly, Saturday's game will be only the second Premier League fixture to have been played at five different venues, with previous meetings taking place at St Mary's, The Dell, White Hart Lane and Wembley.
Recent form: WDLDWL
Recent form (all competitions): LDWDLL
Southampton have also struggled with consistency this season and they currently sit 13th in the league table having taken seven points from their opening six games.
However, their midweek win over Portsmouth will have been a boon to the whole squad, not just because of how well they played but because of that fixture's significance.
The confidence taken from that win certainly puts them in good stead to take on a Tottenham side who have already lost 10 league games this year and are currently enduring one of their worst spells under Pochettino.
Ward-Prowse scored a free kick in that game and the midfielder will be essential to Saints' hopes of a victory in North London, as he has created more chances and attempted more shots than any other player at the club in the league this season.
Also key will be Spanish defensive midfielder Oriol Romeu, who has been an almost ever-present under Ralph Hasenhuttl for his ability to make tackles and move the ball on quickly - attributes that will be essential in a game like this where the away side will have to absorb a lot of pressure.
The continued absence of summer signing Moussa Djenepo is a blow though, because his direct running and pace has been a menace to opposition defences all season.
While Saints have had much more success against the big teams under Hasenhuttl than they did with Pochettino and Claude Puel, they have just one win in their last 10 visits to London and they have not beaten Spurs away since May 2016.
Recent form: LLWDWL
Recent form (all competitions): WWDWLW
Spurs will be boosted for this game by the likely return of Lloris, while Harry Kane should return after young Irish forward Troy Parrott was given the nod on Tuesday night.
Giovani Lo Celso and Ryan Sessegnon remain the only injury absentees for Pochettino but he faces a selection dilemma in midfield, with next week's Champions League game against Bayern Munich looming on the horizon.
Southampton will definitely be without Djenepo, while backup keeper Alex McCarthy will undergo a late fitness test after picking up a knock against Portsmouth.
Danny Ings's brace in midweek is likely to ensure he keeps his place in the side, with star man Nathan Redmond expected to be restored to the starting lineup.
Tottenham Hotspur possible starting lineup:
Lloris; Foyth, Alderweireld, Vertonghen, Rose; Winks, Ndombele; Lamela, Alli, Son; Kane
Southampton possible starting lineup:
Gunn; Cedric, Danso, Vestergaard, Bertrand; Romeu, Hojbjerg; Redmond, Ward-Prowse; Ings, Adams
Head To Head
Saturday's game will be the 124th competitive meeting between the two clubs, with Spurs currently leading the way with 55 wins to Southampton's 38.
This fixture has been a rather goals-y one in recent seasons, with the last nine editions seeing at least two goals scored, with games this century finishing 7-2, 5-1, 5-0 and 4-0.
One has to go all the way back to January 2001 for the last goalless draw between these teams.
We say: Tottenham 2-1 Southampton
Although Spurs are unlikely to solve all their problems in one game, their defeat in midweek should be enough to spur them on to a winning performance on Saturday, even if Saints cause them a few problems on the break late on.
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