Hihi!! aa it's kinda hard to explain,,
from my personal experience, I've always started with designing the characters first, and then built the story around them
since most my oc designs come from random burst of inspiration xD and with time started developing their stories (cuz I still have a lot of characters I haven't worked on yet sjsfkjs)

so I think you can start by defining the overall genre and mood of your story, for example, if it's a colorful or subdued world, is it ancient, modern?
keeping in mind what the story revolves around, you may want to include elements into the designs that connect them from that topic, etc
for example if it's a fantasy adventure, you might incorporate fantastical elements into your character designs like magic items and such
but maybe you're aiming for a darker setting in the story, so you may want to base your designs with more realistic/natural colors, but maintaining the fantastic elements

also if you already have defined the roles of the characters, consider how their designs can complement their personalities and functions within the story
make them share something in common, like a certain type of clothing or accessories

I can't think of much else ^^" I hope that makes sense!