In my opinion, the biggest challenge in a M&A is managing the integration after the deal is done. To me, the post M&A integration is the most critical phase as it sets the stage for the M&A to materialize. The value creation promise is supposed to start at this phone for the shareholders.
I find that each phase comes with a set of key challenges, and issues not addressed in one phase will significantly impact the changes of success for the subsequent phases. Post merger integration is where many of the challenges often materialize: cultural differences that are difficult to overcome, synergies that do not materialize to the degree anticipated (or even worse, nobody knows if they are materializing because metrics were never agreed upon and in that case the merger will often never be seen as a success in the eyes of the workforce), etc.
In my opinion these challenges are, however, often the result of poor preparation or insufficient attention spend on the foreseeable challenges in previous phases of the M&A: cultural assessments (both of the NewCo and the parent company) were never conducted as part of DD, financial and strategical benefits where severely overestimated and/or metrics never agreed, the right people were not involved or sufficiently allocated in the earlier phases of the M&A and so on. One can never foresee every challenge that will present itself, but sufficient effort spend on preparing for the things that experience tells us will pose a challenge will allow for flexibility to deal with the challenges that we did not see coming during integration.