"Investigators will look at the truck driver's driving and medical records, as well as autopsy results to determine whether any drugs were involved," National Transportation Safety Board spokesman Peter Knudson told ABC affiliate KOLO-TV in Reno.
"They'll also check to make sure railroad lights and crossing gates were working," he added.
According to the Nevada State Police that the driver tried to slow down at the last minute but was unable to stop.
The Nevada Highway Patrol said today that at least five people have died and it is feared that more fatalities will be found as investigators gain further access to the crash site.
Friday investigators had trouble getting access to the smoldering rail cars to discover if they could locate additional survivors or victims.
Nevada Highway Patrol Trooper Dan Lopez told ABC News on Friday that 18 to 20 people were transported to hospitals in buses for treatment.
Local media reported "dozens" of people were hurt, including some carried in helicopters to trauma centers.
Amtrak spokesman Marc Magliari in Oakland, Calif., told The Associated Press that 204 passengers and 14 crew members were aboard the California Zephyr en route from Chicago to Emeryville, Calif., which is about 300 miles west of the crash site.
The preliminary investigation and witness statements indicate the truck driver was going northbound on U.S. 95 and the gates were operational and flashing before the collision. Witnesses said it appeared that the driver tried to slow down at the last minute but couldn't.
What remains confusing is that witnesses indicate that at least the signal gates there were working, although it's unclear whether the signal lights were working as well, investigators said.
The NTSB dispatched a "go-team" to investigate Friday's accident.
A passenger on board the train described to ABC News what happened when the truck hit the train, which was believed to be traveling at nearly 80 miles an hour.
"We were driving along on the train and apparently a truck decided that it was going to run the stop out in the middle of the desert -- nothing out here for miles," Jim Bickley told ABC News. "[It] hit the side of the Amtrak car. It was a coach car with people in it.
"My wife and I were in the fourth car, the observation car," he said. "We felt a jolt and a big ball of flames went by the left window with a bunch of black smoke. People yelled.
"There was a lot of smoke so we decided to stick our head out of one of the doors and saw the train on fire," Bickley said.
Passenger Celia Levaca was with her young son in the train car that the truck hit.
"My son's the only thing I grabbed when everything happened," Levaca said. "Everything happened so fast."
Two of the rail cars caught fire as passersby on the highway stopped to help. Local and state police and rescue squads rushed to the scene. A nearby Naval air station also sent helicopters to help evacuate the injured.
The accident at 11:20 a.m. PT Friday shut down a section of U.S. 95 between Interstate 80 and Fallon, Nev.
Amtrak set up a phone number where friends and family of people aboard the train could seek information -- 800-523-9101.
Collisions at rail crossings are not uncommon. Safety groups estimate that a train in the United States collides with a person or vehicle nearly every three hours.
In 2010 there were more than 2,000 collisions between vehicles and trains at railroad crossings, according to Operation LifeSafer.
ABC News Radio and The Associated Press contributed to this report.