In the phrasal adjective star-crossed, cross carries the relatively rare sense to betray or thwart, and star refers to the astrological belief that stars guide people’s destinies. So star-crossed means opposed by fate or destined to misfortune.
The phrase apparently comes from a line in Shakespeare’s Romeo and Juliet:
From forth the fatal loins of these two foes,
A pair of star-cross’d lovers take their life.
As far as we know, there are no recorded instances of star-crossed from before Shakespeare, so there’s a good chance it’s his coinage.
In modern usage, star-crossed lovers is a common phrase—for example:
According to Love, that story is not going to be the tumultuous, star-crossed relationship between Kurt and Courtney. [Guardian]
It’s a story of star-crossed lovers, who are kept apart by their friends and family, but will do whatever it takes to be together. [ABC15]
But star-crossed also appears, without lovers, as a synonym of ill-fated or beleaguered—for example:
For the first time in the franchise’s star-crossed history, the Saints (2-1) have opened the season by scoring 30 or more points in each game. [USA Today]
As one would expect love begins to blossom, but complications inevitably ensue for the star-crossed couple. [Stark Insider]
That star-crossed Southern man never really found his rightful place in the musical landscape before dying semi-young. [The Morton Report]