The Artemis II mission will be the first to the moon since 1972, sending astronauts farther into deep space than humans have ever traveled.
Despite all the preparations, safety systems and redundancies, the nature of human spaceflight is inherently risky, some experts told ABC News.
"I think it'd make everybody feel comfortable to say that all the risk was knocked down to zero," Danny Olivas, former NASA astronaut and engineer, told ABC News. "The truth is it is not and never will be."
For Artemis II, NASA leaders have emphasized that the mission is a flight test because it is the first time a crew will fly on the selected rocket configuration.
"We do everything we can to bring risk as close to zero as we possibly can," NASA Administrator Jared Isaacman told ABC News. "But at some point, when you're exploring the worlds beyond ours, there are some risks worth taking."
NASA is using the 10-day mission to test a variety of systems, including communications and the life support systems for the crew. Olivas said that, for astronauts, the risks that come with space exploration -- especially a test flight -- are understood and accepted.
He added that Artemis II, like any human spaceflight mission, is filled with mitigated risks supported by years of testing and lots of learning along the way
"From an astronaut perspective, that's all taken into account," Olivas explained.
NASA is using a variety of tools and systems to ensure crew safety from launch to splashdown:
Lifesaving suits
The crew of four will be wearing customized spacesuits called Orion Crew Survival System (OCCS) suits from launch through re-entry into Earth's atmosphere.
The bright orange suits -- paired with large, helmeted visors -- create the very well-known astronaut silhouette.
NASA switched from white suits to bright orange suits in 1988 to make astronauts easier to spot during splashdown recovery from the ocean. The Artemis II suits are fire-resistant, have cooling capabilities and protect against depressurization, according to NASA.
The suits can also provide breathable air while removing carbon dioxide, keeping astronauts alive for up to about six days in emergency situations.
Launch Abort System
The Launch Abort System is the 44-foot-tall structure emerging out of the top of the Orion spacecraft. It's designed for worst-case scenarios during liftoff.
According to NASA, if something goes wrong with the rocket, three powerful motors can quickly pull the crew capsule away and carry the astronauts to safety within seconds.
Radiation monitoring
Once Orion leaves Earth's protective magnetic field, astronauts are exposed to higher levels of space radiation.
There are six radiation sensors inside the Orion spacecraft. They each form part of NASA's Hybrid Electronic Radiation Assessor system, which measures radiation dose rates in different parts of the cabin.
Astronauts also have personal radiation trackers that can alert them if radiation levels are too high.
Staying in contact
To stay in contact with the spacecraft, NASA uses multiple communication systems, including the Deep Space Network, NASA's international array of giant radio antennas, and the Near Space Network, made up of Earth-based ground stations and a fleet of space relay.
The overlapping systems help ensure that if one connection drops, the other can reinstate communication.
The only expected blackout is about 41 minutes when the spacecraft passes behind the moon, according to NASA.
Emergency egress system
In the event of an emergency on the launch pad, astronauts and nearby crew can quickly escape using a cable system, similar to a ski lift, that can carry them away from the rocket.
Built-in path home
Part of the Artemis II mission's design includes a free-return trajectory, which is a flight path that relies on gravity to slingshot the Orion spacecraft around the moon and back towards Earth with minimal propulsion.
NASA calls it a "built-in safety net" if the main engines fail. The concept dates back to the Apollo missions and helped save the lives of the astronauts onboard Apollo 13 in 1970 after an oxygen tank exploded, disabling its electrical and life-support system.