(A meta one) The fact Wolverine was killed off a month after Kamala teamed up with him.
The final issue of the Last Days arc and the first volume as a whole really pulls out all the stops, from character resolutions, tying up loose ends, and of course, seeing how Kamala and her cast face the Incursion of Secret Wars.
Issue #10: Bruno is hospitalized after a botched attempt to break a classmate out of the detainment facility of the Cadets who are enforcing Captain Marvel's predictive justice program in Jersey City. Not only is his life hanging by a thread, but the doctors say that even if he pulls through, he'll have permanent paralysis in his dominant hand. And later in the issue, Kamala is around to see it when his vitals start crashing.
Issue #11: Bruno finally wakes up from his injures, but he blames Kamala for everything that has happened to him. He bitterly tells Kamala he's going to salvage whatever he could of his life in Wakanda and he doesn't want to see her again.
The ending of Civil War II #5: Ulysses shows everyone that in the near future, Miles Morales will kill Steve Rogers (who unbeknownst to the heroes, is actually a mole for HYDRA). Kamala rushes to Miles as he drops to his knees, and desperately tries to assure him that Ulysses' vision is not going to come true. Carol then steps in and puts her hand on Kamala's shoulder, before informing Miles that he's under arrest. The issue ends with Kamala shaking and sobbing as she watches one of her closest friends get arrested by her idol.
Post-Secret Empire, the revelation of Josh falling into villainy has left her so jaded that she didn't put on the outfit for some time. She dismissed seeing Bruno on television and receiving an award, her brother has moved out of their home, and in general she sees herself as old news. Ultimately, Red Dagger accidentally stealing her thunder causes her to just up and disappear, jaded by it all.
After giving an Anguished Declaration of Love to Nakia, Zoe tearfully asks if Nakia hates her now, because she would really want to die in this case. Nakia immediately reassures her that no, she doesn't hate Zoe at all, she only doesn't love her this way. No matter the orientation, being afraid of rejection and being let down - albeit gently - is so viscerally human and hurtful.
And the morning after, when Zoe quietly cries while people are deriding her sexuality in the high school's corridors - the worst scenario after coming out, and she was forced. She really, really needed that hug afterwards.