The 28 year old posted the best score for the second day running to open a four stroke lead over fellow European Tour Member Angel Cabrera - the two-time Major champion carding a second straight 69.
Ricardo Gonzalez (71) and Paulo Pinto (72) trail the leader by six in a two-way tie for the third spot at Cordoba Golf Club.
"I didn't strike the ball well early," said Romero, who bogeyed the fourth and fifth holes. "At the sixth I sank a critical putt for par and then I birdied the seventh to take control. I definitely owe it to my putter today."
Romero claimed full control back with four more birdies at the 8th, 12th, 16th and 17th.
Cabrera said: "I'll be the first in charge of containing him. I can't allow him to extend his lead any further. If he does, it's going to be extremely hard on Sunday."
Gonzalez, who will join Romero and Cabrera in the last group out, could have made it to the top himself earlier in the day. He was leading the tournament at eight under par through 14 holes, but double-bogeyed the 15th and bogeyed the last two.
"I played amazing through 14 holes, but then I got distracted at the 15th. I got tired or lost focus, I just don't know. It was a poor and unexpected way to finish, but I'm still in the hunt," said the three-time European Tour champion.