import re

text = "Hello_Dear_Today_is_Nice_Today_is_Nice"

def replace_nth(text, sub, rep_sub, n):
    if n > 1:
        sub = rf'^(.*(?:{sub}.*?){{{n - 1}}}){sub}'
        rep_sub = r'\1' + rep_sub
    return re.sub(sub, rep_sub, text, count=1)

print(replace_nth(text, "Today", "Today_2", 2))