How Could You Leave Us is a song of pain, resentfulness, and reflection about his mother and her drug addiction.

"Yo, I don't know what it's like to be addicted to pills"
His mother is taking pills, and is stuck, addicted.

"I'm in a room with a parent that I don't barely know"
He's losing touch with her and feels so far away, even next to her.

"I guess pills are more important, all you have to say is no"
He doesn't understand how she can't stop.

"Why do I feel like I lost something that I never had?"
Apparently, during his life she didn't have as much touch with him as her wished. One of NF's other songs, Nate, says that...

"Remember back when Mom picked us up from Grandma's house? And she hid her boyfriend in the trunk and drove a couple miles? Down the street, and then she pulled over to let him out. 'Cause she ain't want Dad to know she had these type of dudes around"

...his mother wasn't the most faithful person in the world.

"I know you're gone but I can still feel you"
He's grasping the memories he has, trying not to think about the fact that she isn't who and where she used to be.

"They found you on the floor, I could tell you felt hollow
Gave everything you had plus your life to them pill bottles
You gave everything you had plus your life to them pill bottles
Don't know if you hear me or not, but if you're still watching, why..?"
Eventually his mother let go -died-, leaving him here, alone.