Born at Pesaro, Francesco Maria was the son of Guidobaldo II della Rovere, Duke of Urbino, Count of Montefeltro and Vittoria Farnese, Princess of Parma.

However, Federico died in 1623 from an epileptic attack, leaving only a daughter, Vittoria Della Rovere, wife of Ferdinando II de' Medici, Grand Duke of Tuscany; their child was Cosimo III de' Medici, Grand Duke of Tuscany; none of Cosimo III's children had heirs.

[1] The aging Francesco Maria took up the title of Duke again, but as there was no more hope for a male heir, he gave his Duchy to Pope Urban VIII in 1625.

The Pope's nephew Taddeo Barberini took control of the duchy which was annexed to the Papal States after Francesco's death at Urbania in 1631.

The last member of the della Rovere family, Vittoria, inherited the Duke's art collection and had it transferred to Florence to the Uffizi Gallery.