The title is short for "She Who Must Be Obeyed", the title bestowed upon the sorceress Ayesha by the tribe she has enslaved. (The phrase has passed into British popular culture as the name by which John Mortimer's character Horace Rumpole refers to his wife.)
In the original novel, Ayesha is selfish and amoral, caring nothing for the feelings or even the lives of others so long as she gets what she wants. In a sequel, Ayesha (1905), and a prequel, Wisdom's Daughter, Haggard attempted to reform her character, apparently uncomfortable with having such an unsympathetic character at the centre of the series.
She has been adapted to film many times, including a 1965 Hammer Horror version starring Ursula Andress as Ayesha and John Richardson as her reincarnated love, with Peter Cushing and Bernard Cribbins as other members of the expedition.