The two aid workers were dragged from the home they rented in Multan late Thursday, bringing to six the number of Westerners kidnapped in Pakistan since July.
"The kidnappers have made no contact so far," Azhar Akram, the head of the police investigation team told AFP from Multan.
Masked gunmen snatched the two aid workers, but left behind a guard and a Western woman also staying at the house.
"It could be a simple case of kidnapping for ransom, an extremist group may be involved or may be linked to some personal issue," he added.
The German and Italian had been working for a year to help rehabilitate villagers affected by devastating floods in 2010.
Another member of the police team confirmed that suspicion was falling on extremists.
"The gunmen are believed to have taken them to Khyber Pakhtunkhwa province or some tribal town" in the lawless region on Afghan border," he told AFP on condition of anonymity because he was not authorised to speak to the media.
On Sunday, a Kenyan aid worker also went missing with his Pakistani driver. Police fear the pair have also been kidnapped.
Earlier this month, gunmen kidnapped a British man working for the International Committee of the Red Cross in Pakistan's insurgency-hit southwestern province of Balochistan.
Last August, an American development director, Warren Weinstein, 70, was snatched from his home in Lahore and in July a Swiss couple were kidnapped while driving through Balochistan.
The Taliban claim to have the Swiss. Al Qaeda leader Ayman alZawahiri claims to be holding Weinstein, but the terror group has released no proof.
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Its getting more and more unsafe day by day. I myself with European traits should be more careful. If this continues to happen, Pakistan will eventually loose all its potential investors and other foreigners that come for trade purposes. Sadly, Pakistan has already lost most of its tourist in the northern mountainous areas.