An epic and fiery atmosphere is expected and the Naples locals will look to put on such a show that Los Blancos feel intimidated, even with an athletics track in between the pitch and the stands.
The fact that the official 60,000 capacity it expected to be surpassed - nobody in the city doubts it will reach something close to 70,000 - should also trouble the visitors from Spain, even if Zinedine Zidane and Dani Carvajal insisted during their pre-match press conference that they are not worried about the atmosphere.
Marek Hamsik insisted in his own pre-match interview that the home support would play a role and announced the noise would even reach Turin, while former Napoli captain Giuseppe Bruscolotti was similarly excited about the influence the fans could have.
"The Stadio San Paolo will not fail," he assured MARCA.
Real Madrid have been on the receiving end of hostility ever since they touched down in Naples on Monday, but the decibel levels should peak when the ball gets rolling at 20:45 CET on Tuesday evening.
Zidane: First leg advantage cannot affect Real Madrid's mindset against Napoli
Although Real Madrid went into their Champions League second leg away to Napoli with a 3-1 advantage, Zinedine Zidane is keen for his players to keep their focus in the vibrant Stadio San Paolo atmosphere.
Knowing that the last-16 tie can be turned on it's head in the blink of an eye on Tuesday night, the former midfielder is hoping that Los Blancos use their experience and ignore the scoreboard until the final whistle.
"[The lead] does not change anything, we cannot alter our mindset," the Frenchman noted to his pre-match press conference in Italy.
"Whether we are drawing, or even three or two or one goals up, it cannot change our attitude. It is important for us to keep the mindset that we've had so far.
"We always go out and play our game and try to win."
The Partenopei are a fierce side under Maurizio Sarri and the Italian's opposite number was honest in his assessment of Napoli as a difficult team to face in their own back garden, for a number of reasons.
"I'm not worried, I know that we are playing against a great team," he added. "Tomorrow there will be some brave players out there and we'll see a great match, but we have our game plan.
"I think that, for them that start will be very intense as we know they have to score.
"They are a team that can press high up and then affect us elsewhere on the pitch, they know how to play and tomorrow we'll see how this game turns out.
"As a player [this type of atmosphere in the stadium] was never easy, it is a ground where the fans are behind their team and they are very involved. But at the same time it is very beautiful, I like the places where fans pressure you and back their team. "
Asked about whether he will go with Real's BBC or not, the coach insisted that every player will be important to their quest for both LaLiga and the Champions League.
"Everyone can say what they prefer," Zidane said.
"What I have to do, and what I'm happy to do, is to utilise the whole squad, that's the most important thing.
"We are in two meetings and we want to try to win everything that we can now.
"The goal, because we are Real Madrid, is always to try to win a competition, I will not choose one over the other."
Arsenal face the truly impossible comeback
A seventh consecutive elimination from the Champions League at the last-16 stage will greet Arsenal on Tuesday night unless they can spark an immeasurable fight back against Bayern Munich in their second leg.
Having been humiliated to the tune of a 5-1 scoreline in Bavaria last month, the Gunners are hoping to at least scare their Bundesliga opponents in the search of a much needed moral boost.
Three of the last four league games have spelled defeat for Arsenal and their weak showing at Liverpool on Saturday, earning a 3-1 defeat, served only to compound the ill feeling around the Emirates Stadium, much of which is directed at manager Arsene Wenger.
"We are up against the best team in the world and we must show pride and commitment," said a staunch Gunners boss ahead of the tie, after much questioning over a reported fight with Alexis Sanchez.
"It is ideal to score a goal early. Our honor is at stake and we must compete for 90 minutes."
Aaron Ramsey is expected to return to Arsenal, who are without Santi Cazorla, Mesut Ozil, and Mohamed Elneny, whilst Bayern will defend their lead with Rafinha at full-back thanks to Philipp Lahm's suspension.
Sarri: The pressure is all on Real Madrid
With a two-goal deficit to turn around in their game against Real Madrid on Tuesday, Napoli coach, Maurizio Sarri, faced the press to explain his thoughts on the match and how his team would fare against Los Blancos, suggesting that, in fact, the pressure is all on the visitors.
His counterpart, Zinedine Zidane, has already said that he will start with his best XI, meaning that the hosts will need to play an almost perfect game to progress to the quarter-finals.
Sarri highlighted the need for an intimidating atmosphere at the Stadio San Paolo as a starting point.
"The atmosphere must serve to help us and not to influence Real, because they are accustomed to big games," he began.
"What matters then is what is satisfied on the pitch.
"To see the eyes of the opponent who wants to give everything and not be fearful."
Dries Mertens remains a key player for the Partnopei and Sarri was quick to clear up any injury worries.
"He could be assessed better on Monday, but I think it was just a hint of cramp," he continued.
Though it's the hosts who have to go after the game, the Napoli coach thinks their opponents will feel more under pressure.
"The pressure is all on them, they are the world champions and the richest club in the world," Sarri noted.
"Real have listed 46 consecutive games, but we can make it difficult."
With Napoli losing so many balls against Roma in front of their area, Sarri was asked if it was their weak point?
"Roma press in higher areas," he said.
"But that's the way we play, and in any case they didn't score until the 89th minute.
"There are risks when you have fast strikers in front of you, the same risk that we will have on Tuesday.
"But it's up to us to measure that risk."
James Rodriguez and Real Madrid: Friends forever?
The current state of play between James Rodriguez and Real Madrid is as bright and perfect as ever, despite a number of run-ins between the player and the club's hierarchy.
Suddenly, after the revelations over his desire to leave in January, there is talk of Blancos officials wanting the midfielder to stay put not just until the summer but for the years to come.
Perhaps the key sign in this was that Rodriguez's complaints have always been handled with maximum delicacy by Real, withh guaranteeing his commitment to Madrid causing the priority over seeking a profit on his 80 million euro transfer fee.
The fact that Florentino Perez moved heaven and earth to sign the Colombian from Monaco in the first place is another pointer to Los Merengues' desire for James to succeed, as the president believes he has every component necessary to be a superstar at Estadio Santiago Bernabeu.
What's more is the playmaker's support that comes from his teammates. Gareth Bale, Cristiano Ronaldo, and Karim Benzema are all happy to play alongside Rodriguez and revel in his vision and technique that can unlock defenses at will.
However, there is one last key party in determining just how successful James can be at Real, and that is the man himself.
For the first time in a long time, the 25-year-old is talking positively about his chances of forcing his way into a permanent spot in Zinedine Zidane's starting XI, and this optimism is being reinforced by those higher up at the club.
All in all, this remarkable turnaround has shown all the signs of making Rodriguez's stay in Madrid far more joyous and far more permanent than ever strange possible just a couple of short months ago.