Germany, three-time European champions and runners-up in the World Cup final two years ago, have had a poor build-up to the European Championship leaking soft goals to lose 5-1 to Romania and 2-0 to Hungary.
The intense rivalry between the Dutch and the Germans will put Rudi Voeller's men under even more pressure and Van Nistelrooy is the man to exploit any weakness.
However, Dutch coach Dick Advocaat knows his side are likely to be just as vulnerable as the Germans when they meet in their Group D match at the Dragao Stadium.
Beaten 1-0 at home by Ireland in their last warm-up friendly a week ago, the Dutch have been as tense as usual before a big tournament. The mood has not been helped by a worrying hamstring injury that could see midfielder Clarence Seedorf sidelined.
For once, a competitive international between two of the world's biggest footballing nations who have one of the fiercest rivalries in the sport is all about survival rather than glory.
With the dangerous Czech Republic and outsiders Latvia lurking in the same group, defeat on Tuesday could signal a swift departure for the losers.
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Voeller, however, was confident Germany would rise to the occasion and live up once again to their reputation as the ultimate tournament specialists.
"It is true that we have not played that well over the past year but we are well prepared for this. We will be hard to beat and that goes for the Netherlands and any other team."
Voeller, likely to play with a 4-5-1 formation with Kevin Kuranyi as a lone striker to counter the Dutch 4-3-3 attacking threat, can rely on a fully fit squad.
Advocaat laughed off Germany's worries, telling reporters: "They are a big footballing country, yet they are always trying to portray themselves as the underdogs".
He is far too experienced for those kind of mind games and knows another epic but nervy encounter is likely to add a new chapter to the rivalry that was forged with West Germany's 2-1 win over the Netherlands in the 1974 World Cup final.
Apart from Seedorf, Advocaat has 22 fit players. If Seedorf fails to recover in time, Wesley Sneijder will start. The 19-year-old Ajax Amsterdam midfielder has vast potential but lacks international experience.
Probable teams:
Germany: (4-5-1): 1-Oliver Kahn; 3-Arne Friedrich, 4-Christian Woerns, 5-Jens Nowotny, 21-Philipp Lahm; 19-Bernd Schneider, 6-Frank Baumann, 8-Dietmar Hamann, 13-Michael Ballack, 22-Torsten Frings; 10-Kevin Kuranyi.
Netherlands (4-3-3): 1-Edwin van der Sar; 2-Michael Reiziger, 4-Wilfred Bouma, 3-Jaap Stam, 5-Giovanni van Bronckhorst; 8-Edgar Davids, 6-Philip Cocu, 14-Wesley Sneijder; 7-Andy Van der Meyde; 11-Rafael van der Vaart, 10-Ruud van Nistelrooy.
Referee: Anders Frisk (Sweden)
Linesmen: Kenneth Petersson (Sweden), Peter Ekstrom (Sweden)