"I cannot just expect anything natural any more," the "Modern Family" star says in the new issue of Harper's Bazaar Arabia.
"We'll see what happens. It's not something that doesn't let us sleep. But it's not something I am completely opposed to. … I don't think you can think about it seriously when you're already 43-years-old. It is what it is," she admits.
Sofia, who has a 23-year-old son, Manolo, from a previous relationship, has said in the past she's told Joe it's "now or never" with regard to kids.
"I think the energy levels you have when you're in your 20s cannot be compared to the energy you have at 40," she says. "So of course it's going to be different, but it's possible."
Should a baby be in Sofia and Joe's future, the actress admits that because of her work schedule, she'd probably need to hire help at home -- something she didn't have to stress over when she was raising Manolo.
"I was a single mother for a long time and he always supported and helped me, made it easy to be able to work. I never had to worry about him," Sofia recalls. "When you have a problem all the time, you are unable to be creative and think. As a single mother, I was able to do everything I wanted to do."
Meanwhile, Sofia continues to face a lawsuit brought by her ex, Nick Loeb, over the future of embryos the pair had frozen when they were together in the hopes of one day having children.
Angry about her apparent change of heart, Nick wants custody the two embryos they conceived through in vitro fertilization so he can have them implanted in a surrogate while Sofia wants them destroyed.
"When we create embryos for the purpose of life, should we not define them as life, rather than as property? Does one person's desire to avoid biological parenthood (free of any legal obligations) outweigh another's religious beliefs in the sanctity of life and desire to be a parent?" Nick asked in a 2015 op-ed about the situation.
Sofia has said she believes her ex is using the embryo drama for self-promotion. The case is due back in court next month, according to the Daily Mail.