Boasting a 100% record in Group A, the Serie A side confirmed qualification last time out with another spectacular win, while their Scottish counterparts were destroyed 7-1 by Liverpool - the worst home defeat in their history.
Match preview
Having scored a scarcely credible 10 times past Group A rivals Ajax over the past two matchdays, Napoli cruised into the last 16 in style, as their glorious start to the 2022-23 campaign continues apace.
Goals from Hirving Lozano, Giacomo Raspadori and Khvicha Kvaratskhelia were followed by a late strike by returning star striker Victor Osimhen - as if the Neapolitans needed any more attacking weaponry - in a 4-2 win a fortnight ago, which leaves the Serie A leaders in an unassailable position in terms of qualification.
After their most recent success, three of nine players to top the Champions League's leaderboard for combined goals and assists belong to Napoli, with Raspadori (four goals; one assist), Piotr Zielinski (three; two) and Kvaratskhelia (two; three) all being directly involved in five each.
Already through to the knockout stages, Luciano Spalletti's side will be confirmed as group winners if they can complete the double over an ailing Rangers side this week and Liverpool fail to beat Ajax. Even if they only draw and last year's beaten finalists lose, Napoli will secure top spot.
They could now become the first Italian club to win each of their first five group games since Juventus in 2004, and all indications are that there will be no slowing their progress under the wily management of Spalletti.
When, on Sunday, it seemed the Azzurri were set to drop points for the first time since August, Osimhen rose to the occasion at Stadio Olimpico, as his stunning late winner in the Derby del Sole against Roma took their winning run to 11 games and counting. That represents the Campanian club's best streak for 36 years.
Napoli's only previous meeting with their latest prospective victims was on the second day of this season's Champions League campaign - a 3-0 victory at Ibrox - and few would bet against them repeating the dose in Naples.
Formerly known as Stadio San Paolo, before the death of club icon Diego Maradona two years ago, the only British team to win at Napoli's home ground in 15 Champions League fixtures was Manchester City, back in November 2017.
The latest side to try their hand, Rangers, have won just once in 12 European away games against Italian sides in the past, and recent form suggests they will be hard-pushed to improve that dire record.
Losing all four games to date, Giovanni van Bronckhorst's current crop have conceded 16 goals in Group A already. Indeed, through the first four matchdays this year, no team has shipped more.
As a result, the Glasgow club are unable to reach the last 16 but could still finish third and snatch a Europa League spot if they win on Wednesday. However, they will be confirmed in last place if they lose and Ajax do not - or even if they draw and the Dutch side win.
Last term's run to the Europa League final seems ever further away the more Van Bronckhorst's men progress through the current campaign, and the former Feyenoord boss is under severe pressure as he heads south for his side's penultimate group game.
Only John Lundstram's late strike denied Livingston a first-ever victory at Ibrox last weekend, and a 1-1 home draw saw Rangers slip four points behind Old Firm foes Celtic in the Scottish title race. After a performance met with full-time boos, featuring just three shots on target, they must now step up several gears to compete with their fellow Light Blues.
Napoli Champions League form:
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Napoli form (all competitions):
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Rangers Champions League form:
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Rangers form (all competitions):
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Team News
Posing a pleasant problem for Luciano Spalletti to resolve, at the weekend Victor Osimhen scored his second successive winner since returning from injury, but this season's stars - Giovanni Simeone and Napoli's leading Champions League scorer Giacomo Raspadori - are also vying for selection up front.
The hosts' coach will once more be without centre-back Amir Rrahmani, whose recent thigh injury could keep him out until 2023, so Juan Jesus should deputise again, alongside Kim Min-jae.
Though Andre-Frank Zambo Anguissa returned to training last week after a thigh problem of his own, he may not be ready to feature on Wednesday, which would see either Tanguy Ndombele or Eljif Elmas start in midfield.
Joining them should be Piotr Zielinski, and so far in this season's Champions League, only his compatriot Robert Lewandowski has been directly involved in more shots than his tally of 23 (10 attempts, 13 chances created).
Rangers, meanwhile, still have a number of important players sidelined, as John Souttar joins Ryan Jack, Connor Goldson and Sweden international Filip Helander on a long injury list, which also includes Ianis Hagi, Tom Lawrence and Glen Kamara.
At the weekend, Leon King was replaced by James Sands at half time due to illness, while Welsh winger Rabbi Matondo sustained a back injury. Nonetheless, both Alex Lowry and Kemar Roofe recently returned to action and could be involved in the visitors' squad.
Up front, Antonio Colak and Alfredo Morelos battle it out for selection, while at the other end of the pitch, Allan McGregor has faced more shots on target (29) and conceded more goals (12) than any other Champions League goalkeeper this season. In all, McGregor has kept only four clean sheets in 21 career appearances among Europe's elite.
Napoli possible starting lineup:
Meret; Di Lorenzo, Kim, Jesus, Rui; Elmas, Lobotka, Zielinski; Politano, Raspadori, Kvaratskhelia
Rangers possible starting lineup:
McGregor; Tavernier, Sands, Davies, Barisic; Davis, Lundstram; Arfield, Tillman, Kent; Colak