Two-time defending European champions Leinster face the Top 14 giants at Stade Marcel Michelin, where the French club have not lost in over three years.
Both sides are unbeaten thus far in Pool Five, and their meetings this weekend and next will go a long way to deciding who will win the group and guarantee a quarter-final berth.
This will be the fourth consecutive season in which Leinster and Clermont have clashed in the Heineken Cup, but winger Nacewa says familiarity does not make life any easier for the defending champions against a team including the likes of Morgan Parra, Aurelien Rougerie and Julien Bonnaire.
Nacewa told Leinster TV: "They had Parra, Rougerie and all their big names playing last week, as well as a big pack with some big names so they have prepared well to play us.
"This fixture has turned into a bit of a derby over the last few years. I have said they are not a team you want to come up with in the group stages and we have had them twice in the last three years.
"They have an unbelievable squad and every player is a good one. But we have to be confident going there, they have not lost there in going on for 50 home games so we have to focus on how we perform."
The game will also pit Clermont coach Vern Cotter against former cohort Joe Schmidt.
The pair worked together in France before Schmidt elected to make the move to Leinster, and Cotter knows how important these fixtures are if his side are to progress.
"Qualifying from the pool will depend on this double header," said Cotter.
"They, as we have done, have long marked this date in the calendar.
"My players are very excited, focused and motivated by the idea of playing this match."
The hosts are without the key trio of centre Jamie Roberts (hip), full-back Leigh Halfpenny (neck) and lock Bradley Davies (concussion) after they all suffered injuries while on international duty with Wales.
"Only a fortnight ago things were looking very positive for us, when we were welcoming back some key players," he said.
"However, we have been extremely unfortunate to pick up a raft of injuries in the last few weeks.
"It is frustrating that we cannot select from a full strength squad for these crucial matches, but on a positive note, it gives a chance for some of our other players to step up and show what they can do."
In Pool Two Leicester host Treviso looking to record another bonus-point victory to boost their last-eight aspirations, having picked up five points against the Ospreys at Welford Road in October.