The Shrimpers are unbeaten in four matches, while the visitors have gone five consecutive matches without defeat.
Match preview
Southend had to come through an FA Cup qualifying tie against Eastleigh to secure their spot in the first round proper.
The clash against their fellow Nations League side appeared to be heading to a replay until Aribim Pepple netted a 93rd-minute winner to clinch a dramatic victory.
Since getting the better of Eastleigh, Southend have gone on to claim league victories over Rochdale and Tamworth on either side of a goalless draw against Aldershot Town.
Having kept four consecutive clean sheets, the Shrimpers will now look to produce a strong defensive display against football league opposition.
They enter Saturday's fixture with hopes of progressing to the FA Cup second round for the first time since 2018-19.
Charlton have avoided defeat in their last five competitive matches, but they will be frustrated by the fact they have won just two of their previous 10 league games, leaving them in 12th place in League One with four points separating them from the top six.
The Addicks have drawn each of their previous three matches, although last Saturday's clash against Wrexham may have felt like a victory after Matty Godden netted a 97th-minute penalty to salvage a point.
Nathan Jones's side went on to claim a commanding 3-0 victory in Tuesday's EFL Trophy clash against Chelsea Under-21s, making it three games in a row where they have scored at least two goals.
After making it four consecutive home games without defeat, Charlton will look to carry that sort of form onto their travels, having drawn one and lost two of their previous three away matches.
The Addicks will enter Saturday's contest with hopes of progressing to the FA Cup second round for the fourth consecutive season.
Southend United FA Cup form:
W
Southend United form (all competitions):
L
L
W
W
D
W
Charlton Athletic form (all competitions):
L
W
D
D
D
W
Team News
Southend will have to assess Danny Waldron and George Moncur, with the pair looking to prove their fitness in time for Saturday's fixture.
Goalkeeper Collin Andeng-Ndi dropped out of the side for the recent win over Tamworth, but there is a possibility he could return to the starting lineup for the FA Cup tie.
Macaulay Bonne is set to feature against his former club, with the striker poised to feature in a front-two pairing with Pepple.
As for the visitors, they are still unable to call upon the injured trio of Kayne Ramsay, Lloyd Jones, Dan Potts, Daniel Kanu and Chuks Aneke.
Defender Tennai Watson is unlikely to be involved after he was forced off in the opening stages of last Saturday's draw.
Forward Gassan Ahadme recently returned to training, but it is unclear whether he will be available for the first-round tie.
Southend United possible starting lineup:
Andeng-Ndi; Scott-Morriss, Crowther, Taylor, Morton, Ralph; Coker, Husin, Bridge; Bonne, Pepple
Charlton Athletic possible starting lineup:
Mannion; Edmonds-Green, Mitchell, Gillesphey, Edwards; Docherty, Coventry; Anderson, Berry, Campbell; Godden