The trick is media_sideload_image() and set_post_thumbnail(). media_sideload_image() assumes you can grab the URL to the image, whether it exist in /wp-content/ or somewhere else (another site, even). As long as you can programmatically reference the image’s URL, something like this should work.
$image="image.jpg";
$media = media_sideload_image($image, $post->ID);
if(!empty($media) && !is_wp_error($media)){
$args = array(
'post_type' => 'attachment',
'posts_per_page' => 1,
'post_status' => 'any',
'post_parent' => $post->ID
);
// reference new image to set as featured
$attachments = get_posts($args);
if($attachments){
foreach($attachments as $attachment){
set_post_thumbnail($post->ID, $attachment->ID);
// only want one image
break;
}
}
}