Before starting for the East she had met Alexander Pope, and during her absence he wrote her a series of extravagant letters, which appear to have been chiefly exercises in the art of writing gallant epistles. While Pope may have been fascinated by her wit and elegance, Lady Mary's replies to his letters reveal that she was not equally smitten. Very few letters passed between them after Lady Mary's return, and various reasons have been suggested for the subsequent estrangement and violent quarrel. The last of the Istanbul letters to Pope purports to have been written from Dover on 1 November 1718. It contains a parody on Pope's Epitaph on the Lovers Struck by Lightning. The manuscript collection of these letters was passed round a considerable circle, and Pope may have been offended at the circulation of this piece of satire. Jealousy of her friendship with Lord Hervey has also been alleged, but Lady Louisa Stuart says Pope had made Lady Mary a declaration of love, which she had received with an outburst of laughter. In any case Lady Mary always professed complete innocence of all cause of offence in public. She is alluded to in the Dunciad in a passage to which Pope affixed one of his insulting notes. A Pop upon Pope was generally thought to be her work, and Pope thought she was part author of One Epistle to Mr A. Pope (1730).
Pope attacked her again and again, but with especial virulence in a gross couplet in the Imitation of the First Satire of the Second Book of Horace, as Sappho. Verses addressed to an Imitator of Horace by a Lady (1733), a scurrilous reply to these attacks, is generally attributed to the joint efforts of Lady Mary and her sworn ally, Lord Hervey. She had a romantic correspondence with a Frenchman named Rémond, who addressed to her a series of excessively gallant letters before ever seeing her. She invested money for him in South Sea stock at his desire and, as was expressly stated, at his own risk. The value fell to half the price, and he tried to extort the original sum as a debt by a threat of exposing the correspondence to her husband. She seems to have been really alarmed, not at the imputation of gallantry, but lest her husband should discover the extent of her own speculations. This disposes of the second half of Pope's line "Who starves a sister, or forswears a debt" (Epilogue to the Satires, 113), and the first charge is quite devoid of foundation. She did in fact try to rescue her favourite sister, the countess of Mar, who was mentally deranged, from the custody of her brother-in-law, Lord Grange, who had treated his own wife with notorious cruelty, and the slander originated with him.
In 1739 she left her husband and went abroad, and although they continued to write to each other in affectionate and respectful terms, they never met again. Edward worked away from home, leaving Mary to raise their children, and she eventually divorced him. She exchanged many love letters with Francesco Algarotti, Count Algarotti, competing with an equally smitten John Hervey for the Count's affections. The German Count Georg Ludwig Albrecht von Rantzau, although 25 years younger than Lady Mary, almost lost his heart to her as he recounts in his memoirs  published in 1741. But she never remarried.
At Florence in 1740 she visited Horace Walpole, who cherished a great spite against her, and exaggerated her eccentricities into a revolting slovenliness (see Letters, ed. Cunningham, i. 59). As Lady Mary was then in her sixty-third year, the scandalous interpretation put on the matter by Horace Walpole may safely be discarded. She lived at Avignon, at Brescia, at Gottolengo and at Lovere on the Lago d'Iseo. She was disfigured by a painful skin disease, (smallpox), and her sufferings were so acute that she hints at the possibility of madness. She was struck with a terrible fit of sickness while visiting the countess Palazzo and her son, and perhaps her mental condition made restraint necessary.
Her ex-husband spent his last years in hoarding money, and at his death in 1761 is said to have been a millionaire. His extreme parsimony is satirized in Pope's Imitations of Horace (2nd satire of the 2nd book) in the portrait of Avidieu and his wife.
Lady Mary had problems with both her children. Her daughter eloped with a suitor Mary disapproved of, while her son ran away from school repeatedly. After his father’s death, he contested a will in Mary’s name without her knowledge.
Her daughter, whose husband, was now Prime Minister, begged her to return to England. She came to London, and died in the year of her return, on 21 August 1762.