But the grind of making a hit TV show was nothing compared to what she went through off-screen.
In 1985, she narrowly survived a home invasion robbery during which she was raped. Drescher says she forced herself to look at her assailant so she could identify him later. He is still in prison today.
And shortly after "The Nanny" was cancelled, Drescher was diagnosed with uterine cancer.
The treatment left deep scars, inside and out.
"I remember going into the bathroom and looking at my body and seeing how swollen and black-and-blue it was," she said, "and that cruel, red line going across my pubic bone from the hysterectomy. I thought, I'll never be the Nanny. I'll never be that woman again, and, you know, life as I knew it was over."
But Drescher went on to make a full recovery -- a very full recovery.
"Women think, you know, if they had a hysterectomy it doesn't work anymore. And it works great!"
She laughs now, but her cancer came at an especially tough time -- after ending her 21-year marriage to her husband and producing partner.
Smith asked, "How hard was it to make that final break? Because you're the one who did it, you're the one who said, 'It's over.'"
"Yeah, it was like walking through fire," Drescher said. "because I had never done anything at the expense of someone else. And he didn't want it. And he made it tough for me."
And not long afterward, Peter Marc Jacobsen told his former wife that he'd discovered he was gay.