The setting is very surreal. Perspective frequently switches between a "false" fictional world and a "true" real world, however the two influence and bleed into one another. There are multiple timelines and parallel universes, multiple versions of the same character, as well as dreams and hallucinations.
Almost every character is mentally ill in some way. Autism, depression, anxiety, eating disorders, PTSD, OCD, and psychosis are all mentioned or shown.
Child abuse and neglect is implied throughout the entire series, and explicitly stated many times. Nothing explicit is ever shown, but it's prevalent throughout every game and DLC.
No one is actually sexually assaulted on screen to my knowledge but there are mentions of the workers being used for breeding back on Uberia which don't seem entirely consenual given the context and it is also mentioned that Charles was almost sexually assaulted in HC2 in the Vincent vessel.
The main character suggests that someone is suffering from an overdose from a fictional drug. Another instance involves her being drugged and describing her symptoms as being that of an overdose. There are also multiple attempts to commit suicide through overdosing on prescription drugs.
Multiple character can be seen vomiting in a cafeteria and there is vomit on the floor in that specific room. At another part of the game a character will have vomit on their clothes.
The main character can be read as being transgender. She is abusive and violent, but not sexually predatory, and it is not presented as having any connection to her gender.
Suicide is featured very heavily throughout the entire game. Multiple characters kill themselves throughout the game, two of them resulting in permenant deaths. The suicides rang from jumping, drowning, and assaulting one's self with a toothbrush. Suicide is also
The screen sometimes flashes white or red to signify injury or death, but it is done in singular slow flashes and not in a way that could trigger photosensitive epilepsy.
To elaborate on the previous comment, Scarlett is an unborn child and her mother has a son named Charles, in which she refers to as a girl and as Scarlett, because she did not want to abort Scarlett.
Multiple characters who are LGBT+ die, as it is a very death-filled series (this includes practically all letters of the spectrum). However, none of those deaths are singled out or because they're LGBT+, if you're wondering.
A character is forced to get an abortion and it is shown to be traumatic for her, with her obsessing over her unborn daughter and being unable to move on. However, the game doesn't at any point condemn abortion in itself.
The entire game and franchise is full of blood, gore, body horror, and general "fleshy" and gorey aesthetics. It's highly recommended you do not play this game if you cannot handle gore.