The sense of foreboding has been present every time the two names have been in the hat.
For seven years now the heart-rate has quickened until either Pompey or Southampton’s names have been safely separated in knockout competition.
The reason for that, of course, is through the Blues’ demise and subsequent victory in their exhausting fight to remain in existence the distance between the fiercest of footballing foes has become a gaping chasm. On the pitch that is, of course.
Off it, the calibre of the folk who will always be the biggest portion of any club’s identity was being laid bare. And as the fans saved their football club their worth was present for the world to see.
An understanding of the extent of that struggle perhaps explains why the most recent of the competitive meetings between the two clubs was so celebrated in 2012.
Plenty along the M27 could never quite grasp why a draw would be reflected on quite so happily, even factoring in the dramatic late, late leveller from David Norris silencing Southampton on their own doorstep.
But amid the tailspin of Pompey’s fall, the 2-2 draw kept in place that unbeaten run which now stretches back 14 years and factors in the 4-1 wins, which remain arguably the two most memorable modern-era south coast derbies.
Even with the two clubs travelling in opposite directions that sequence was somehow kept intact. And in the conditions being faced back then that was quite something.
Which probably explains why with the club’s wage bills being separated by well over £100m in recent seasons, there wasn’t a great desire to see them cross paths as the Blues regrouped and began plotting their path back. The distance was so vast it may not have been pretty.
There was a spell under Paul Cook’s stewardship where his approach almost seemed more suited to taking on teams from further up the football ladder, a view endorsed by that 48-pass goal against Bournemouth and the scalps of Championship sides Derby and Ipswich being taken.
Still, it would have taken a brave Pompey fan to risk putting that theory to the test against Southampton, even if it was a game craved by the manager back then.
That was a stance echoed by current assistant Joe Gallen, as he gave a cock-a-hoop reaction to news of the draw as it was made minutes after last week’s victory at QPR.
For the rest of us it took a little more time to digest and compute.
The hope had been for the next derby to take place on a more even footing, yet once the work of Andy Hinchcliffe and Don Goodman in pairing the footballing enemies via the platform of the Carabao Cup had permeated the emotions began to ebb and flow.
The initial hesitancy found itself washed over by excitement. Out went reluctance, instead superseded by anticipation.
And it was absorbing the circumstances of the renewal of one of football’s most raw and genuine rivalries which allowed those sentiments to reasonably surface.
Firstly, Pompey’s name being plucked out of the olive-green ball first was significant. Would there have been quite the same fervour in this neck of the Hampshire woods if PO4 wasn’t hosting the third-round meeting?
The first competitive Fratton Park clash under the lights between the clubs in 43 years. It’s a spine-tingling thought. Nothing else needs to be said about what’s coming, mush.
Then consider the notion of the two clubs engaging in this competition's format. That means the match will be played over 90 minutes, before going to penalties if necessary. No extra-time, no replay and played to a decisive outcome.
There’s little doubt that, in a knockout environment, abridged conditions are more suitable for Pompey. The longer a tie plays out, the more the ability and resources of a Premier League club will tell against lower-division opposition.
A slightly more imponderable but nonetheless possibly significant factor is the strength of the side Ralph Hasenhuttl chooses to field. The Austrian has indicated he’s fielding strong teams in knockout action this season, but will also give fringe players a chance.
That was seen as five changes were made for their second-round win at Fulham. Will it be the strongest possible Southampton side fielded at Fratton? It will certainly be Pompey’s, but even so there's the small factor of a few hundred million separating the squads’ values.
It would be nice to glean confidence from Hasenhuttl’s assertion the game ‘is not that interesting’ to his players, but safer to assume a foreign manager instead preaching the mantra of concentrating on the next game in his own way instead.
So, will all those factors be able to level a sloping playing field Pompey will be undoubtedly be kicking up? The reality is a game played in these conditions will invariably still have one outcome - that’s why the bookies have Southampton as odds-on favourites to progress.
But there will be plenty of the Fratton faithful taking the 4/1 price on offer for Pompey to pull off an upset, no doubt.
That’s because assuming the role of underdog and stacking the odds against them is a position which has invariably brought the best out of their club and its followers.
And when you've witnessed the improbable become possible before that's always a valid cause for optimism.