A judge is deciding if there is enough evidence for the case against Seamus Daly, 45, from Jonesborough, County Armagh, to go to a crown court trial.
Mr Daly, originally from the Republic of Ireland, was arrested in April 2014.
The Omagh bomb was the biggest single atrocity in the history of the Troubles in Northern Ireland.
It happened just four months after the Good Friday Agreement was signed.
The death toll included nine children and three generations of one family, but no-one has been convicted in a criminal court of carrying out the attack.
The hearing at Omagh Magistrates' Court is expected to last for two days.
Along with the murder charges, Mr Daly faces charges of causing the explosion and possessing the bomb, and two charges relating to another dissident republican bomb plot in Lisburn, County Antrim, in April 1998.
Previously, all of Mr Daly's magistrates' court hearings in Omagh have been via videolink from prison.
He was brought to court in a prison van on Thursday and was led inside handcuffed to a security officer.
Some relatives of those who were killed in the attack were in the court.
Mr Daly sat a few feet from the victims' relatives who have followed every stage of the long legal process.
After his arrest Mr Daly gave police a statement denying any involvement in the Omagh bombing or Lisburn plot.
His lawyers have argued that the case against him is weak and much of the evidence has been discredited.
A man accused of murdering 29 people in the Real IRA bomb attack in Omagh in 1998 has appeared in court in the County Tyrone town for the first time.