Steve Clarke will be hoping for his new signings to fill the void left by Romelu Lukaku, while Mauricio Pochettino's side looks to improve on last year's relegation battle.
The experienced striker, who has played for five top-flight clubs, including Arsenal, Manchester City and Chelsea, is back in England after an 18-month absence following his arrival at the Midlands club in July.
Anelka is one of three new West Brom signings, with Diego Lugano and promising youngster Matej Vydra also joining from Paris-Saint Germain and Udinese, respectively, with the latter on a season-long loan deal.
And head coach Steve Clarke has already seen the 34-year-old Anelka prove he remains a prolific finisher by netting seven goals in as many preseason friendly games for the club.
The Baggies' boss will be hoping the Frenchman can make an instant impact on his return to the Premier League as West Brom looks to build on last season's eighth-place finish. History is on its side as the club is unbeaten against Southampton at home since May 1984.
But Mauricio Pochettino's men have their own plans, and, after returning to the Premier League after a seven-year absence last season, are targeting a top-10 finish. Southampton have new signings to showcase, too, with Croatia international Dejan Lovren and former Celtic midfielder Victor Wanyama both available to the Argentine ahead of his first full campaign in charge.
Pochettino has a number of injury doubts, though, as he has concerns over young defenders Luke Shaw and Nathaniel Clyne, with the former suffering from a knee injury during a 4-3 friendly win over Real Sociedad on Saturday.
While Pochettino has confirmed that the pair could feature if they train well on Friday, internationals Gaston Ramirez and Maya Yoshida, who played for Uruguay and Japan respectively in Rifu in midweek, will be assessed.
The duo were two of seven Southampton players called up for international duty, but Rickie Lambert, Steven Davis, Artur Boruc, Emmanuel Mayuka and Lovren all came through their Europe-based friendlies unscathed.
West Brom also saw a number of players in action for their respective countries, but while Clarke plans to assess them, he has no major concerns ahead of the fixture.
"At this stage I'm not aware of any injury problems heading into the weekend. The doctor will assess the internationals," Clarke said. "We probably go into the game as slight favorites, whereas last year we kicked off against Liverpool at home and everyone expected them to win.
"This season it's slightly different because the fact we finished eighth last season will mean teams will come to us now and make it difficult for us.
"It's up to us to combat that - we have to find another level."