There’s no way to put it, as Devil May Cry 5 is definitely a difficult platinum trophy/100% achievement list. Not only do you have to beat the game on every difficulty setting, but you also need to get S Ranks on every single mission on all difficulties, excluding one of them. The hardest difficulty, Hell and Hell, makes it so you die in one hit, while enemies have health equivalent to Son of Sparda difficulty. Yes, you even have to S Rank all missions on Hell and Hell.
Step 1 - Play on Human
Since difficulty trophies don’t stack in this game, it’s best to start out playing on Human difficulty. Enemies on this difficulty have normal health and deal normal damage, so you aren’t at any advantage or disadvantage over them. While playing through the game, this’ll be the best opportunity to do all of the collectible trophies/achievements. This means getting all of the Blue Orbs/Fragments, Purple Orbs/Fregments, and even the Secret Missions. It’s also a good idea to go after some of the mission-specific trophies/achievements during this one, like killing all enemies in the first mission, as an example.
While not entirely important, you can also start working on getting S Ranks at this time. Human difficulty has fairly lenient requirements for getting S Ranks, so some of them will come without you even trying. The most important thing to remember is to not use any continues, as that will provide you with a 1.2x multiplier at the end of the mission. Considering this is likely your first playthrough, getting the No Hit bonus is out of the question, but that nets you a higher multiplier and pretty much guarantees the S Rank. You can always come back later to get the S Ranks, once you’ve gotten used to the controls and enemies.
Step 2 - Play on Devil Hunter
As already mentioned, difficulty trophies don’t stack in this game, so you will be playing on Devil Hunter for the second step. This one is the same as Human difficulty, except enemies have twice as much health and deal twice as much damage. Nothing is different in terms of enemies, aside from the above, so you will be pretty much doing the same thing as the last playthrough.
Step 3 - Play on Son of Sparda & Skills
Things will definitely start ramping up in difficulty with Son of Sparda, which is unlocked by completing the game once. Enemies have four times the health than on Human, plus they also deal four times the damage. In addition to this, you will start noticing different enemy spawns throughout the game. In fact, the first change you will find is that an Empusa Queen spawns during the Prologue, so you have an idea on how this difficulty works. Note that you unlock a new skill for Dante by beating this difficulty, which is required for the all skills trophy/achievement for him.
Also, you will want to replay this mode a few times, just to get used to how the enemies work and to get familiarized with the missions, as Hell and Hell is pretty much this, but with a one-hit kill mechanic for you. Once you complete this difficulty, it’s the perfect opportunity to start farming Red Orbs to purchase all of the skills. The last checkpoint in Mission 13, with the Dr. Faust weapon, is one of the best places to farm Red Orbs. Make sure you have the Dr. Faust 4 upgrade, along with Hat Trick, then drop down the hole to an area with some nests and a lot of enemies. Hold R1/RB, then press Circle/B to rake in the orbs. You can restart the checkpoint when you have a few enemies left.
Note that this can be done on Human difficulty to make things easier on you, in case you get hit some. It will likely take a few hours to get the necessary orbs for all skills, but this is probably the best farming spot for Red Orbs in the game. You will definitely want as many skills, or all of them, before diving into the next difficulty.
Step 4 - Play on Dante Must Die
Well, you’re looking at one of the harder difficulties in the game, as enemies have eight times the health than Human, plus they do eight times the damage. You will also get the same enemy spawns as on Son of Sparda, and enemies will definitely be very aggressive. Hopefully, you heeded the warning from the last step and farmed the necessary Red Orbs to get all of the skills, as you will need them here. If you didn’t die much on the previous difficulties, then you might start dying a lot here. Don’t worry about using Gold Orbs for reviving here, at least at first, and just get used to things.
Step 5 - Play on Heaven or Hell
This difficulty will provide a pretty short playthrough, as everything dies in one hit, enemies and your characters alike. This includes the bosses, too, so you can just hang back and use ranged attacks to deal with everything. If you couldn’t get the trophy/achievement for beating the boss in the Prologue, this is your best chance to do it now.
Step 6 - Play on Hell and Hell
Welcome to the hardest difficulty in the game, Hell and Hell, where you die in one hit and enemies have the same health as on Son of Sparda. To add to this, there are no checkpoints and you only have three lives here, as you cannot use Gold Orbs or pay with Red Orbs to revive. That basically means if you get hit three times during a mission, you will be forced to restart from the beginning of the mission. Getting S Ranks on this difficulty is probably the hardest thing in the game, but it is possible to get them even if you get hit twice, so there is a little bit of leeway. Luckily, the S Ranks seem to have the same score requirements as on Son of Sparda.
Step 7 - Cleaning Up
You’ve done pretty much everything at this point, so it’s time to just clean up the rest of the trophies/achievements at this point. This will include getting the rest of the S Ranks on all difficulties, other than Heaven or Hell, as well as any miscellaneous trophies you haven’t gotten yet.