The attack was another reminder of the risks to women educators and aid workers from Islamic militants who oppose their work. It was in the same conservative province where militants shot and seriously wounded 15-year-old Malala Yousufzai, an outspoken young activist for girls' education, in October.
There was no immediate claim of responsibility for the latest shootings.
The teachers and health workers one man and one woman were killed in Khyber Pakhtunkhwa province on their way home from a community center in the town of Swabi where they were employed at a medical clinic and primary school. Their driver was also injured.
Javed Akhtar, the director of Support With Working Solution, said the medical clinic vaccinated children against polio, and many of the NGO's staff had taken part in immunization campaigns.
Militants in the province have blown up schools and killed female educators. They have also kidnapped and killed aid workers, viewing them as promoting a foreign, liberal agenda.
Khyber Pakhtunkhwa province, formerly called the Northwest Frontier province, borders the tribal areas of Pakistan along the frontier with Afghanistan to the west. Militant groups such as the Taliban have used the tribal areas as a stronghold from which to wage war both in Afghanistan and against the Pakistani government. Often that violence has spilled over into Khyber Pakhtunkhwa province.
In 2007, the Taliban led by Maulana Fazlullah took over the scenic Swat Valley, marking the height of their strength there. The Pakistani military later pushed the militant group from the valley, but the Taliban has repeatedly tried to reassert itself.
The injured driver in Swabi told investigators that the gunmen stopped the vehicle and removed a boy the son of one of the women before indiscriminately opening fire, said police officer Fazal Malik. The woman's husband rushed to the scene after receiving a phone call alerting him to the shooting.
"I left everything and rushed towards the spot. As I reached there I saw their dead bodies were inside the vehicle and he (his son) was sitting with someone," said Zain ul Hadi.
Swabi police chief Abdur Rasheed said most of the women killed were between the ages of 20 and 22. He said four gunmen on two motorcycles fled the scene and have not been apprehended.
The NGO conducts education and health programs and runs the community center in Swabi, Akhtar said. The group has been active in the city since 1992, and started the Ujala Community Welfare Center in 2010, he added. Ujala means "light" in Urdu.
The center is financed by the Pakistani government's Poverty Alleviation Program and a German organization, said Akhtar.
He said the NGO also runs health and education projects in the South Waziristan tribal area, as well as health projects in the cities of Tank and Dera Ismail Khan and the regions of Lower Dir and Upper Kurram. All of those cities and regions are in northwest Pakistan, the area that has been most affected by the ongoing fight with militants opposed to the government.
Aid groups such as Support With Working Solution often play a vital role in many areas of Pakistan where the government has been unable to provide services such as medical clinics or schools.
Many aid groups that also work in the region are already familiar with the persistent threat militant groups pose, but the scale and viciousness of Tuesday's attack worried even veteran campaigners.
Maryam Bibi, who founded an organization called Khwendo Kor, which carries out education and development programs in Khyber Pakhtunkhwa and the nearby tribal areas, said she and many of her employees live in fear that they will be targeted next.
"I'm really very worried now because our girls go to the field. Our work is in the villages," said Bibi. She said many of the female employees of such organizations are already under pressure from family and a culture that frowns on women working outside the home and mixing with men.
"On top of that, they're shot dead," she said.
In some areas like the northwest, aid groups have had to work to overcome community fears that they are promoting a foreign agenda at odds with local traditions and values.
But many residents in Swabi said the school and medical center provided a vital service to the community, and they mourned those who were killed.
Murad Khan said his daughter was studying at the primary school, which provided free books and uniforms to students. He said many people in the area are worried that the school and clinic will close.
"This school is like a gift for all of us, the poor people of the village," he said. "People in our area are sad."
The NGO director said all projects will be suspended as security measures are reviewed but he vowed that they would resume their work soon.
He said the NGO had not received any threats before the attack.
In the southern city of Karachi, officials said four people were killed when a bomb in a parked motorcycle exploded amid a crowd of buses for political workers returning from the rally held by the Muttahida Qaumi Movement. The MQM is the dominant political party in Karachi.
There was no immediate claim of responsibility for the attack.
Saghir Ahmed, the provincial health minister, said that in addition to the dead, 41 people were injured.