Spurs finished fourth in the table last season and are therefore preparing for a return to the Champions League, while Southampton were 15th, just five points clear of the relegation zone.
Tottenham won four of their final five Premier League games of the 2021-22 campaign to claim fourth position in the table ahead of Arsenal, ultimately finishing two points clear of the Gunners in fifth, with Antonio Conte's side managing to secure a spot in the group stage of this season's Champions League.
Spurs were only actually three points behind third-place Chelsea, and the North London club will be looking to again challenge high up the table this season, potentially seeing themselves as the best of the rest behind Manchester City and Liverpool, who could go head-to-head for the title again.
Tottenham have not been overly busy this summer in terms of matches, playing just four friendlies in total, including a 1-0 defeat to Roma in their final pre-season fixture last weekend.
Conte's side have been active in the transfer market, though, bringing in Richarlison, Yves Bissouma, Djed Spence, Ivan Perisic and Fraser Forster, while Clement Lenglet has arrived on loan from Barcelona.
Tottenham had the fourth-best home record in the Premier League last season, picking up 40 points from 19 matches, and they will be looking to make the perfect start to their 2022-23 campaign, especially as their next fixture is the small matter of a London derby with Chelsea on August 14.
Southampton, meanwhile, finished 15th in the Premier League table last season, which was also their position in 2020-21; the Saints were 11th in 2019-20 but have been 17th, 16th, 15th and 15th in four of their campaigns since an excellent 2016-17 season saw them claim eighth.
Ralph Hasenhuttl's side only won nine of their 38 league games last season and were just five points clear of the relegation zone, so the club's supporters will be expecting improvement this term.
Southampton, who lost their final four league matches of last season, have played five friendlies this summer, with their only victory coming against Monaco on July 27, and they will enter this contest off the back of a 2-1 home defeat to Villarreal last weekend.
The Saints have been busy during the summer market, bringing in Gavin Bazunu, Sekou Mara, Romeo Lavia, Armel Bella-Kotchap, Joe Aribo and Mateusz Lis, but there have been a couple of notable departures on free transfers in the shape of Forster and Shane Long.
Hasenhuttl's side have a difficult opening month of the campaign, also taking on Leeds United, Leicester City, Manchester United and Chelsea in their first five matches, so there is a chance that they could be in a lowly position in the table heading into September.
Tottenham will be without the services of new signing Richarlison on Saturday due to a suspension, while Oliver Skipp is definitely out of the contest due to a foot fracture.
New signing Bissouma is also a doubt, with Conte insisting during his press conference that he would not take any risks when it comes to the midfielder, who still has a chance of being in the squad.
Tino Livramento is also a long-term absentee, meaning that the Saints will be missing three players on Saturday.
Che Adams could lead the attack despite the recent speculation surrounding his future, with new signing Mara potentially starting on the bench.
Bazunu could be given the nod between the sticks, though, while there might be another debutant in the shape of Aribo, who has arrived from Rangers this summer.
Tottenham Hotspur possible starting lineup:
Lloris; Romero, Dier, Davies; Doherty, Hojbjerg, Bentancur, Sessegnon; Kulusevski, Kane, Son
Southampton possible starting lineup:
Bazunu; Walker-Peters, Salisu, Bednarek, Perraud; S Armstrong, Ward-Prowse, Romeu, Elyounoussi; Aribo; Adams
We say: Tottenham Hotspur 3-1 Southampton
This is a tough opener for Southampton, and we are finding it very difficult to predict anything other than a defeat for the Saints. Tottenham were strong towards the end of last season and look in good shape for the 2022-23 campaign, so we can only see a comfortable home victory here.
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