First of all, for score based achievement and especially for this one, we need to undestand how the game calculate the score of the run.

The score is only calculated for each fight and only take into account the loss of life during the fights, never between them. So you can loose it between fight (events purpose) without loosing any point.

For the fights, the based score is 30 500 points shared as follow :

• 1000 (1st floor)
  
• 1500 (2nd floor)
  
• 3000 (3rd floor - Daedalus)
  
  
• 2000 (4th floor)
  
• 3000 (5th floor)
  
• 6000 (6th floor - Fel)
  
  
• 5000 (7th floor)
  
• 9000 (8th floor - Seraph)

To these values, you have to add :

• 50% of the based score for the 1st, 2nd, 4th, 5th and 7th floors if you activate the challenge
  
• 10% per round left, for all stages, if you kill the boss earlier

Note that you will have a penalty (applied in percent to the based score) if your hearth took damage during a fight (and only during a fight)

Finally, you have to add you remaning gold at the end of the run to know your final score.

What is really important is :

• Best activate all challenges but especially the last ones :
  For exemple, you will earn 500 points with the 1st floor challenge but 2500 within the 7th floor !
  
  
• The earlier you kill Seraph, the best reward you will have :
  If you kill Seraphin with 3 rounds left, the bonus will be 2700 points which is quite even to
  4 rounds left for Fel (2400 points) and
  8 rounds left for Daedalus (again 2400 points)

Around 50% of the total score of a run is represented by the two last fights !

A good roadmap exemple can be :

• 1800 (challenge activated and 3 rounds left - 80% bonus)
  
• 2700 (challenge activated and 3 rounds left - 80% bonus)
  
• 3900 for the Daedalus' fight (3 rounds left - 30% bonus)
  
  
• 3600 (challenge activated and 3 rounds left - 80% bonus)
  
• 5400 (challenge activated and 3 rounds left - 80% bonus)
  
• 8400 for the Fel's fight (4 rounds left - 40% bonus)
  
  
• 9000 (challenge activated and 3 rounds left - 80% bonus)
  
• 15300 for the last fight (7 rounds left - 70% bonus)

Without considering any gold, you would hit 50 100 points at the end of the run.

It's just an exemple, but remember that it's not really a problem to do less scoring on 1st and 2nd floors since you do more on Fel and Seraph's fights.

For exemple, on my personnal attempt, I only kill the boss of the 2nd floor with 2 turns left and challenge activated for a 70% bonus but keep some gold to do more points and particularly killed Seraph with 8 turns left.

You can reach 50 000 points whenever you want since you can try indefinitely the daily challenge to validate the acchievement.
But if you see more player than usually (around 5 people after 6 hours and 10 people at the end of the challenge) above 50 000 points, it implies that the daily challenge is easier.

Remember these two facts :

• You have to activate most of the challenges but 1st and maybe 2nd ones can be optional if you do more points on Fel and Seraph's Fights
  
• Remember that your main goal is to kill Seraph as early as possible (7 or 8 turns left), that's the real key !

If you have difficulties to reach 50 000 points, you can also do the following :

• Do yourself the whole run a first time and learn the keys of the run :
  Which unit do I need to recruit or not, which upgrades will I need, when, which road taken...
  
  
• Optionnaly, after your first run, you will have access to the build of top players, search for some build which match yours (not especially the first one) and try to understand how to optimize your run

Good Luck, Enjoy and Have Fun