The epicenter Saturday was near the popular tourist town of Pokhara, where foreigners embark to trek through a majestic stretch of the Himalayas. The quake badly damaged buildings, including treasured landmarks at the country's capital Kathmandu.
Nepal is no stranger to natural disasters with landslides and avalanches punctuating its mountainous terrain. And there are many challenges in the rescue efforts.
The focus of the rescue operations has been on rescuing people entangled in the rubble.
"The next 72 hours are critical in addressing injuries caused directly by the earthquake," said Garrett Ingoglia, vice president of emergency programs at AmeriCares, which is sending an assessment team with medical supplies to Nepal.
After the first three days, the chances of finding survivors decreases.
"There are cases (in which) people survive under rubble," Ingoglia said, but it's dependent on oxygen supply and water.
The leading injuries and causes of death after an earthquake are crush injuries, blunt trauma and infected wounds.
The aftershocks and unstable structures are making rescue efforts extremely risky for emergency medical workers, he said.
In the Haiti earthquake in 2010, one of the major medical emergencies were deaths from a condition associated with crush injuries called rhabdomyolysis
. This occurs when muscles have been crushed and ruptures, leading to kidney failure.
There's also the risk that with so many people with massive, traumatic injuries, "sometimes relatively minor injuries don't get attention and become more serious," Ingoglia said.
Access to food, water and shelter remains a challenge.
In Kathmandu, a home to about 1 million people, residents have nowhere to go, as many of their homes have collapsed and people have resorted to sleeping outdoors
Kashish Das Shrestha, a Kathmandu resident, said stores are running out of food and especially water. "It's going to become more and more difficult. It's challenging because stores have run out of water."
Another huge challenge is logistics, as highlighted by the United Nations in a situations report.
Nepal has a notoriously mountainous terrain, in which scraggly, rocky roads circle around giant hills, wide enough for only one car to squeeze by.
On regular days, access in and out of towns can easily be obstructed by rock falls and potholes -- but an earthquake can completely choke access.
The Nepali government has requested international assistance, especially heavy equipment for rubble removal and helicopters for transport and access to blocked areas. Requests for help have been made to China and India, which sent a Super Hercules plane on Saturday. American disaster response teams are on their way, according to the U.S. Embassy in Nepal.
The worst-struck regions are located in the mountainous, difficult-to-reach areas in the western and central region. Sindulpalchowk, a district where over 150 people died last year in a major landslide was also one of the worst-hit areas, according to a U.N. situations report.
In Nepal's mountainous and remote regions, accessing phone and data services can also be challenging -- adding to the panic as family members tried to reach their loved ones.
Tragedy strikes Everest again
Another challenging environment to rescue people is the Everest region.
The earthquake triggered an avalanche at Mount Everest during its climbing season, leaving at least 13 killed and an unknown number injured. The season started this month, after the 2014 season was canceled following 16 deaths caused by an avalanche.
Everest Base Camp, where the climbers prep for their journey, appeared to be the site of many of the deaths. It is based in a circle of mountains with hanging ice cliffs all around it, said Kenton Cool, a climber who spoke with people at base camp.
Because of the high altitude, it's unclear how quickly the Everest victims can be helicoptered out for medical treatment.
"Some of the safest areas have been higher on the mountain," Cool said, based on communication he had with people at the mountain.