I swear you could not make this shit up if you tried:
[W]hat's inspired the title is, 50 and G-Unit are putting on a sold-out performance somewhere in a fictional Middle Eastern setting. This is where the 'blood on the sand' comes in. They put on the performance; the people are pleased, but the concert promoter stiffs them and doesn't give 50 and G-Unit their payment.
So, of course, 50 isn't going to leave until he gets paid, so he hassles the concert promoter, [saying] if he doesn't come up with the money now, there will be consequences. And instead, the promoter offers him a very valuable gift – something that's valuable to this particular country – a diamond encrusted skull.
So 50 gets the skull, and as he's about to leave this war-torn country, when they're ambushed and the skull is taken. They escape the ambush, but they're without the skull. So 50's motivated to get what belongs to him. So basically, throughout the game, he's trying to track these people down and find out who they are and why he was ambushed.