I will most likely have PCs ready to head south to tackle the undead menace following rise of tiamat.
Do you think the adventures could be scaled up to challenge 16th level PCs?
Sometimes you cant just make monsters tougher - especially when it is about bypassing traps etc..
I think the only part of
Tomb of Annihilation that would be challenging to 16th level PCs is the Tomb of the Nine Gods. You'd want to enforce the PCs getting sealed within the Tomb and eliminate any easy methods for leaving (e.g.
gaseous form through cracks in ceiling to surface on Level One). You'll want to be very clear about & strictly enforce the magical conditions in the Tomb. I'd also personally make long resting a terrible idea: have the night hags dream haunt PCs attempting to long rest in a
Leomund's tiny hut, have all traps be reset, and have Withers send a tomb guardian after them (maybe use a medium-sized Iron Golem or monster from
Mordenkainen's Tome of Foes like an eidolon or medium-sized Nightwalker). These combine to make the dungeon about attrition and managing their resources. Make it a one-day dungeon assault, essentially, rather than a drawn out multi-month adventure with hexcrawling.
And you may want to consider giving most traps the False Appearance trait shared by gargoyles, mimics, and other monsters. Players who've run their PCs to high level tend to be very genre savvy and develop a trap sixth sense, making it tricky for a DM to find that sweet spot of being sporting/fair with descriptions & maintaining the sense of mystery. My rule of thumb is "Perception checks detect
triggers, not
traps. Describe what they
sense."
While you can enjoy role-playing Port Nyanzaru, some of the zanier situations in the jungle, Omu, and the Fane – but none of them will challenge a 16th-level party (at least as written). Get them to the Tomb ASAP. Maybe a session where they do research to learn about the magical conditions in the Tomb (ToA p.128), are plagued by a night hag haunting one of their dreams (remember that reduction in maximum HP can't be cured while the Death Curse persists!), and then teleporting right into Omu and quickly gathering puzzle cubes. I'd implement some reason why they only have 1 day to gather the puzzle cubes...maybe the cubes teleport back to their respective shrines in the light of dawn? That makes it a little more challenging and serves as a quick warm-up for the Tomb.
I'd also encourage reading up on Acererak and deciding if/how you want to modify his stats or strategies. While many advocate changing his spell selection, personally I like it a lot and the spells lend themselves to creative use. That said if you want him dropping
delayed blast fireball during
time stop, go for it. What I'd change up is his strategy. Instead of appearing only after the atropal is destroyed, have him appear when the atropal is reduced to half hit points or less. I'd also give the lich phylacteries a role to play – letting him drain them to use as "bennies" allowing him to tweak his spellcasting a bit, such as using
mage hand at longer than normal range to seal the Skeleton Gate behind the PCs. And remember that he can cast
animate dead as a legendary action (and upcast it at that!), so skeletons should be pouring from the north wall ossuary alcoves...you might make these minotaur skeletons for your 16th-level party. Also consider that one of Acererak's strongest defensive capabilities (
wall of force) may be easily handled by a 16th-level party with access to
disintegrate.