The winner arrived after 22 minutes when Philip Cocu's long pass reached central defender Andre Ooijer and his header found Van Nistelrooy who converted the chance.
Coach Marco van Basten started with Robin van Persie on the right flank and the in-form Arsenal man proved a handful for the Cameroon defence throughout the match.
He earlier combined with Mark van Bommel to create a chance for Van Nistelrooy, whose close-range effort was saved by Idriss Kameni, and he was involved again when the keeper denied Cocu.
"In the first half hour we showed how we wanted to play and that it's possible," Van Basten told a news conference.
"We played against high calibre opponents and forced them into our game plan and created several chances."
"This style takes a lot of energy and can't be played for 90 minutes so our change of pace could be better. We'll try to use this style at the World Cup. It has to prove if it will work."
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Cameroon, who failed to qualify for the World Cup finals, had Alioum Saidou sent off late on.
The Dutch face Mexico on Thursday and Australia three days later in their final friendlies before kicking off their World Cup campaign against Serbia and Montenegro on June 11.