The Welsh outfit saw out a draw against Rafa Benitez's men at the Liberty Stadium last week and will be quietly confident of progressing in their debut season in the Europa League
Garry Monk's charges turned in one of their best performances of the season against Rafa Benitez's side to give themselves a fighting chance heading to the Stadio San Paolo.
Indeed, the only thing missing from the Welsh side's display was a goal - something they will be looking to rectify in Italy.
After watching his side fail to score against Napoli in a match they could have won, Monk then saw Swansea put three past Liverpool on Sunday only to frustratingly lose late on as the Anfield club recorded a 4-3 win in their Premier League clash.
Napoli - third-placed in Serie A - might have some concerns about their form, having followed up the draw in south Wales with a 1-1 draw at home to Genoa in the Italian top flight.
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"It is not a physical issue at all," he said. "The team is good and all staff are involved in both the championship and Coppa Italia - the players know they have to distribute energy.
"Swansea played a great game against Liverpool in the weekend's Premier League fixtures, despite losing a very close contest.
"They could make things very difficult. We must be prepared to go the distance."
Swansea will be looking to make it into the last 16 for the first time in their history, while Napoli lost out to Viktoria Plzen at this stage last year, suffering a 5-0 aggregate defeat.
Napoli are likely to have Pepe Reina in goal after Rafael picked up a knee injury in the first leg.
The Swans, meanwhile, could hand a start to Jonjo Shelvey, who made a goalscoring Premier League return from a hamstring injury against his former club at Anfield at the weekend.
However, doubts remain over the fitness of attacker Michu, who has been sidelined with an ankle injury since December.
In Michu's absence, Wilfried Bony has shouldered greater responsibility for Swansea and the Dutch forward heads to Italy in good form, having scored twice at Liverpool to take his tally for the season to 19 in all competitions.