CapnZapp
Legend
Running Tomb of Annihilation as a hexcrawl at higher level
Here's what I've got so far. Input welcome!
/Zapp
Avoid the “race” triggered by the Death Curse as per the book and the Syndra quest
For me, an enjoyable hexcrawl assumes you actually enjoy exploration for its own sake.
Having a timer goes directly counter to this goal – it means your players will want to skip encounters and hurry things along. So change the Death Curse and delay Syndra's quest. This allows “breadth first” mapping as opposed to “depth-first”. That is, the “following cool leads and go wherever we fancy” exploration strategy as opposed to “we should probably ignore everything that distracts us from our goal”.
Simplify and streamline the daily procedure.
If you run Tomb of Annihilation as written, you and your players can easily end up having to make a lot of rolls each game day...:
Thanks to the Legendary Pants blog for summarizing most of this info
2x d20 for rain, 1x d100 if heavy rain
3x d20 for random encounters, 1x d100 per random encounter
1x ability check for navigation, 1x d6 if lost
1x exhaustion Con save if dehydrated per PC, 1x exhaustion Con save if taking a forced march per PC
...and up to 3 saves against disease per PC
I can only speak for my group, but we would dearly want to to focus on the adventure and its encounters, and we think D&D features plenty of die rolls as it is already.
So it would be great if we could do away with the mundane rolls regarding water and disease. A simple spell will take care of them anyway. Let's focus on the fun stuff – exploration and encounters!
Restrictions on Heavy Armor (and clothing)
I simply don't see any 5th level character having to make any Exhaustion checks because they didn't drink enough, and so I don't see how the restriction on heavy armor comes into effect either. It's just a lot of words with zero practical impact.
Instead I suggest a character wearing heavy armor (or clothing) for a full day is always considered to have at least one level of Exhaustion. It is simply impossible to get rid of the last level without doffing the armor (or casting magic such as Endure Elements).
Have the Curse deny long rests
This suggestion has multiple functions.
First, level 5 characters need more of a challenge than merely collecting water, applying bug salve and the like. The jungle challenges as explained by the book are trivial as soon as you leave the training levels. Restricting long rests has in comparison a real impact.
Second, I prefer to introduce restrictions that put the focus on enduring despite them. Not restrictions that encourage the “how should we circumvent or disable this?” metagame. In other words, draw player focus away from “which spells can we cast to ignore additional limitations?” and onto “okay, so these additional limitations are part of the game. How can we win despite them?”. The point isn't to encourage players to find ways to play the game as usual, the point is that this campaign is different and challenging.
Third, as you probably know, the game simply works better when you have more than 0-3 encounters per long rest. With free long rests, encounters need to be individually challenging since the resource management mini-game is put out of commission. And if the encounters are individually challenging (for 5th level characters), that makes it implausible that so many of the NPC explorers and inhabitants are still alive. So instead of making everything more dangerous and having to rewrite the random encounter tables entirely, we instead restrict long rests , achieving one of the game's fundamental assumptions and retaining plausibility on NPC presence to boot!
Let the Curse put the focus on the player characters
Don't have the Curse prevent raising dead player characters from the dead. Instead embrace how this makes the Curse so much more personal, when it is the player character's clock that starts to tick! In other words, I would suggest Raise Dead works on anyone – once. The wasting disease still works as written, only now it's personal.
If no PC dies until late in the campaign, feel free to increase the HP maximum loss to d4 per day. And of course, if no PC have died, you can always introduce Syndra and her quest if the party needs a gentle push in the direction of the Tomb.
Provide clues and leads
At first, you need to motivate the PCs to enter the jungle at all. The players might dive into the hexcrawl, but their players still need some reason to go there.
Later on, you need to be in control over the breadcrumbs leading to Omu. Ideally I should be able to present several strings of leads, but I'm not there yet. The book itself is of very little help, unfortunately. Ideally, you have a fairly complete grasp before you get very far of what leads there are and how they are interconnected, so there always is something for you to entice a player group with when they lose steam or become lost.
Here's what I've got so far. Input welcome!
/Zapp
Avoid the “race” triggered by the Death Curse as per the book and the Syndra quest
For me, an enjoyable hexcrawl assumes you actually enjoy exploration for its own sake.
Having a timer goes directly counter to this goal – it means your players will want to skip encounters and hurry things along. So change the Death Curse and delay Syndra's quest. This allows “breadth first” mapping as opposed to “depth-first”. That is, the “following cool leads and go wherever we fancy” exploration strategy as opposed to “we should probably ignore everything that distracts us from our goal”.
Simplify and streamline the daily procedure.
If you run Tomb of Annihilation as written, you and your players can easily end up having to make a lot of rolls each game day...:
Thanks to the Legendary Pants blog for summarizing most of this info
2x d20 for rain, 1x d100 if heavy rain
3x d20 for random encounters, 1x d100 per random encounter
1x ability check for navigation, 1x d6 if lost
1x exhaustion Con save if dehydrated per PC, 1x exhaustion Con save if taking a forced march per PC
...and up to 3 saves against disease per PC

I can only speak for my group, but we would dearly want to to focus on the adventure and its encounters, and we think D&D features plenty of die rolls as it is already.
So it would be great if we could do away with the mundane rolls regarding water and disease. A simple spell will take care of them anyway. Let's focus on the fun stuff – exploration and encounters!
Restrictions on Heavy Armor (and clothing)
I simply don't see any 5th level character having to make any Exhaustion checks because they didn't drink enough, and so I don't see how the restriction on heavy armor comes into effect either. It's just a lot of words with zero practical impact.
Instead I suggest a character wearing heavy armor (or clothing) for a full day is always considered to have at least one level of Exhaustion. It is simply impossible to get rid of the last level without doffing the armor (or casting magic such as Endure Elements).
Have the Curse deny long rests
This suggestion has multiple functions.
First, level 5 characters need more of a challenge than merely collecting water, applying bug salve and the like. The jungle challenges as explained by the book are trivial as soon as you leave the training levels. Restricting long rests has in comparison a real impact.
Second, I prefer to introduce restrictions that put the focus on enduring despite them. Not restrictions that encourage the “how should we circumvent or disable this?” metagame. In other words, draw player focus away from “which spells can we cast to ignore additional limitations?” and onto “okay, so these additional limitations are part of the game. How can we win despite them?”. The point isn't to encourage players to find ways to play the game as usual, the point is that this campaign is different and challenging.
Third, as you probably know, the game simply works better when you have more than 0-3 encounters per long rest. With free long rests, encounters need to be individually challenging since the resource management mini-game is put out of commission. And if the encounters are individually challenging (for 5th level characters), that makes it implausible that so many of the NPC explorers and inhabitants are still alive. So instead of making everything more dangerous and having to rewrite the random encounter tables entirely, we instead restrict long rests , achieving one of the game's fundamental assumptions and retaining plausibility on NPC presence to boot!
Let the Curse put the focus on the player characters
Don't have the Curse prevent raising dead player characters from the dead. Instead embrace how this makes the Curse so much more personal, when it is the player character's clock that starts to tick! In other words, I would suggest Raise Dead works on anyone – once. The wasting disease still works as written, only now it's personal.
If no PC dies until late in the campaign, feel free to increase the HP maximum loss to d4 per day. And of course, if no PC have died, you can always introduce Syndra and her quest if the party needs a gentle push in the direction of the Tomb.
Provide clues and leads
At first, you need to motivate the PCs to enter the jungle at all. The players might dive into the hexcrawl, but their players still need some reason to go there.
Later on, you need to be in control over the breadcrumbs leading to Omu. Ideally I should be able to present several strings of leads, but I'm not there yet. The book itself is of very little help, unfortunately. Ideally, you have a fairly complete grasp before you get very far of what leads there are and how they are interconnected, so there always is something for you to entice a player group with when they lose steam or become lost.
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