The 41-year-old Lewis is set to die by injection at 9 p.m. Thursday at Greensville Correctional Center in Jarratt. The U.S. Supreme Court and Gov. Bob McDonnell have refused to intervene.
Lewis is being executed for the October 2002 hired killings of her husband and stepson to collect on a $250,000 insurance policy.
Prosecutors said she enticed two men to carry out the killings through sex, cash and a promised cut of the insurance money.
The two triggermen were sentenced to life in prison. One committed suicide in 2006.
Lewis has leaned on her faith as her execution nears, and so has her stepdaughter - the sole surviving child of the man whose murder Lewis arranged.
"The Bible tells you, if you sinned, if you break the law, you have to be punished for it," said Cathy Clifton, the daughter of Julian Clifton Lewis, who was slain in October 2002 along with his son, Charles. Clifton plans to witness her stepmother's death.
"She did a crime and now she has to pay for it," said Cathy Clifton, who was 30 when she lost her father and baby brother. She plans to travel from Pittsylvania County to attend the execution with her husband, her sister-in-law and her best friend.
Prosecutors said she plied two men she met at a Wal-Mart with money and sex to carry out the killings so she could collect a $250,000 insurance payment. Her husband and stepson had to die for her to collect.
The U.S. Supreme Court refused to block her execution Tuesday, and Gov. Bob McDonnell has declined two requests for clemency from her attorneys. Aside from making another appeal to McDonnell, Lewis has run out of options, her attorney said.
On the eve of her execution, Lewis was meeting with the Rev. Lynn Litchfield, who has known her since she entered the Virginia correctional system and has become one of her staunchest allies.
Lewis' execution would be the first of a woman in Virginia since 1912. Texas held the most recent U.S. execution of a woman in 2005.
Out of more than 1,200 people put to death since the U.S. Supreme Court reinstated capital punishment in 1976, only 11 have been women.
Lewis' impending execution has stirred extraordinary attention in a state that is second only to Texas in the number of people it executes. Lewis' gender and questions about her role in the killings have elevated interest in her case. Her attorneys have also questioned how a woman they call borderline mentally retarded could mastermind two killings.
Thousands have written to the governor's office to protest the planned execution. Opponents have included The European Union, which made an "urgent appeal" to McDonnell to spare Lewis the death penalty.
Iranian President Mahmoud Ahmadinejad accused the West of launching a "heavy propaganda" campaign against the case of an Iranian woman who was sentenced to be stoned to death for adultery but failing to react with outrage over the imminent execution of Lewis.
McDonnell, who rejected Lewis' bid for clemency on Friday, said he thoroughly reviewed the case and found no reason to commute her sentence to life in prison.
Advocates contend her gender and questions about her role in the murders ultimately will undermine the use of the death penalty, which they argue should be reserved for the "worst of the worst."
"I think this case is going to leave a bad taste," said Richard Dieter, executive director of the Death Penalty Information Center. "This is a case where fairness and mercy would support clemency, but it wasn't done."
Lewis' supporters note that one of the killers, Matthew Shallenberger, later claimed he was the mastermind and manipulated Lewis to get some of the insurance money. Shallenberger committed suicide in prison in 2006. He and the other hired killer, Rodney Fuller, were sentenced to life for the killings.
Cathy Clifton and others supporting Lewis' execution say her cold-blooded actions justify the ultimate penalty.
Lewis arranged for Fuller to have sex with her 16-year-old daughter. Julian Lewis lay mortally wounded from several shotgun blasts for an hour before she called police. She took his wallet from his pants as he lay bleeding.
"She was very cruel throughout," Cathy Clifton said. She also doesn't buy the claim her stepmother lacked the smarts to mastermind the crime.
"She's not the smartest person I met, but in no way, shape or form is she mentally retarded. She manipulated people."
Lewis admits she was no angel.
"I was doing drugs, stealing, lying and having several affairs," she wrote of her past in a testimonial delivered in August to her fellow inmates.
"After being sentenced to death in June of 2003," she wrote, "I have done nothing but trust Jesus and let him into my heart, mind, soul!"
The prosecutor who secured Lewis' murder convictions and sheriff's deputies who investigated the case are expected to witness the execution.