Python making call list for C++ executable
Putting an open() function inside a list comprehension seems a bit iffy to me, especially since you don't seem to close it anywhere.

List comprehensions are generally better than for loops.

The config_file name is a bit misleading, as it's the filename, not the file object.

So alternative code would be:

config_file_name = directory + file_prefix + ".txt"
with  open(config_file_name) as config_file:
    config_list_split = [config_item for config in config_file for config_item in config.split()]


This is less transparent, but performance-wise I would expect it to be better than a for-loop.