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."
In Pool Six, injury ravaged Cardiff Blues face an uphill task to keep alive their slim qualification hopes against Montpellier at the Arms Park.
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.
Michael Paterson, Dan Fish, Andi Kyriacou and Tom James are also absent, leaving director of rugby Phil Davies in an unenviable position.
"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.
Gilbert has released a new line of rugby cleats. The Gilbert Virtuo 8S is part of the exciting new product. Check it out.
The entire All Blacks apparel line has been updated for 2013/14. Check out the New Zealand All Blacks polo.
The Nike Tiempo is a solid rugby cleat and one of few styles still made from full-grain natural leather.
The Gilbert Blitz 8S rugby cleat is a great cleat at a great price of $69.99. Get a new pair of cleats today.
A cool looking all black rugby cleat with the high performance adidas is known for. Get in the Gear!
Wear the crest of the British and Irish Lions on your t-shirt. A great look for the summer.
The All Blacks Performance t-shirt is black with hints of blue from the training jersey. Very Cool.
The New Zealand All Blacks training jersey for 2013/14. Get in the Gear!
The USA Rugby Pro Alternate rugby jersey is perfect for any fan of the Eagles. Get yours to wear during the summer Test matches.
The NEW All Blacks 2013/14 jersey has arrived at World Rugby Shop. Dare to wear the colors of the All Blacks.