Thursday's clash sees Benitez - a Champions League winner and twice victorious in Europe's second-tier club competition - pit his wits against a managerial novice, as Monk makes his first foray into European competition.
Benitez won the UEFA Cup with Valencia in 2004 and the Europa League as Chelsea's interim coach last season, while his crowning glory came in 2005 when Liverpool famously overcame Milan in the Champions League final in Istanbul.
He is bidding to become the first coach to win the Europa League, in its various incarnations, with three different clubs, while his counterpart takes charge of just his fourth match.
A former Swansea captain, Monk was chosen as the man to replace Michael Laudrup when the Dane was sacked earlier this month and has enjoyed a mixed start to his time in charge.
Having registered a 3-0 win over rivals Cardiff City in his first game, Swansea then picked up a point at Stoke City before bowing out of the FA Cup at Everton on Sunday.
Conversely, Napoli have lost just once in their last 11 Serie A matches and remain in contention for a cup double in Benitez's first season - with Juventus' dominance making a league challenge unlikely.
The Spaniard has guided his side to third in the table and into the final of the Coppa Italia, but will consider them unfortunate to have missed out on the Champions League knockout stages.
Napoli amassed 12 points from the group stage to finish level with Borussia Dortmund and Arsenal but had to settle for third spot owing to an inferior head-to-head record against their German and English rivals.
However, Benitez is focused on securing Napoli's first European silverware since the UEFA Cup triumph in 1989.
"We expect a tough game because it will be very important to keep the ball," Benitez said.
"We will be thinking about how to give the maximum in the UEFA Europa League, seeking the highest possible goals for the club."
Swansea qualified from Group A in their first continental competition since bowing out of the 1991-92 European Cup Winners' Cup in the first round to Monaco.
Under the guidance of former boss Laudrup, they finished second in qualifying behind Valencia but will now face one of the tougher opponents left in the competition.
In what will be Swansea's first meeting with an Italian side, Monk has concerns over forward Michu (ankle) and midfielder Jonjo Shelvey (hamstring), while Benitez has no fresh injury worries to contend with.
