Saints looked set for the fourth round after Nathan Redmond's double gave the Premier League side a 2-0 lead against the Rams in the original meeting but Frank Lampard's men fought back to take the tie back to Hampshire.
Wednesday's winners face a trip to Wham Stadium to meet Accrington Stanley in round four.
Southampton won their first fixture in five at the weekend when they defeated Leicester City at King Power Stadium and Ralph Hasenhuttl's men are 13/20 (1.65) favourites with William Hill to follow up with victory on home soil against the Rams.
The same firm go 27/10 (3.70) that the tie remains level at the end of 90 minutes.
Both managers have other priorities and, so, neither side is expected to be at full-strength. Shane Long scored his first goal since April against Leicester at the weekend and will be keen to get amongst the goals again should he feature here.
Derby's joint top scorer this season, Harry Wilson, has missed the last two matches with a hip injury and remains doubtful so may not be risked against Saints.
Derby have failed to keep a clean sheet in their last eight ties in this competition.
Saints have scored more than one goal in each of their last four wins inside 90 minutes. William Hill offer 7/10 (1.70) that Hasenhutl's side score two or more goals in this match.
Saints have developed a habit of starting quickly under their new manager, scoring first in five of their last seven matches.
William Hill's 6/5 (2.20) quote, then, for the hosts to have the lead at the break could represent real value for punters here.