Alan Pardew is looking for his side to take advantage of a Charlton team still smarting from an F.A Cup defeat at the weekend.
The Saints manager believes the hosts can build on their league display at the Valley in September, and will be further boosted by facing opposition who are on the back of a bad result.
"We were playing well just prior to that league game, and we took that form into that match. I felt we should have won the game, but a draw was still a good result," he said.
"They are a good side with a few good individual players who are on the back of a terrible result at the weekend so hopefully, we can capitalise on that.
"Phil Parkinson will have taken it badly, so he will be looking for a reaction from his players on Wednesday night. We have to expect that."
Saints are presently in a good run of form, but Pardew kept his cards close to his chest regarding the sort of team he will field this evening.
"Take away the Bristol Rovers defeat and that is thirteen games with just the one defeat, so it's the sort of run that we should be on. It's the sort of form we should be hitting as we have a good team with good players. It's important that everyone stays fit, and for this game everyone is fit.
"I don't really like to change a winning side, but at some point along the road here we can't expect every player to play in each game, so we may have to rest one or two, maybe mark one or two that their performances have to be better.
"The way to do that is to change the side from time to time. We changed it to great success last week, so we will have to wait and see what team I put out on Wednesday night, but I believe we will have 13,000 fans turning up, so we have a duty to them and to the Club to win this game. I will pick the strongest team to win this game."
The Londoner is, however all too aware of the threats that his former side will possess on the night.
"They have a strong group who have been together for a couple of years now. There are some good players there and they are just trying to find that winning formula again, they went on that fantastic run at the start of the year. If they get back to that they will get promoted so that's what Phil and the team will be searching for.
"Jonjo Shelvey is one of the best young players outside the Premiership, Bailey scores goals from midfield and I think the whole midfield really is a level above this. They have a very strong midfield, so that's an area we need to be good in."
Pardew re-affirmed that his side will be in it to win it as he continues to push for as much success as possible on all fronts this season.
"We have got three options of getting to Wembley, the playoffs, this competition and the FA Cup, so we have to aim high.
"This is a competition that I think we have a good chance of winning, there are no Championship clubs, no Premiership clubs, only the teams that are in and around us. We are a good team who are playing well, so we want to go far in it and we hopefully win it."
