The series will not return for a third run, according to Broadcast.
Monroe - which first aired in March 2011 - starred Irish actor Nesbitt as Dr Gabriel Monroe, a maverick neurosurgeon.
Sarah Parish and Tom Riley also appeared in the series, created by Blackpool and Occupation writer Peter Bowker.
The show premiered with 6.85 million viewers on ITV1 last year, but ended its second run with an overnight audience of 3.53m earlier this month.
Nesbitt previously claimed that Monroe would appeal to viewers because the show tells "human stories".
"I think we're fascinated by characters like [Monroe], who have a brilliance that we don't possess but also have very human flaws which we all recognise," he said.
> James Nesbitt Monroe Q&A
> James Nesbitt: 'Monroe is different to House'
Watch a trailer for Monroe below: