The Northern Approach
There are a number of paths to reach Mysidia, all of which feature nasty Monsters to contend with. The most straightforward path from Fynn is to head southwest, following a narrow land bridge west of Altair. Once you see a lake emptying into a river, head due south and you should see Mysidia. The downside to this path is that it takes you through the area Near the Mysidian Tower, which has the most dangerous Monsters on the World Map.
Almost every Monster that appears here is new. Werewolves are the most common. Their four attacks cause Poison, which will rob you of likely stat advancement if not evaded or removed with Esuna, but otherwise are pretty typical tough physical opponents that lack Elemental weaknesses. They are sometimes accompanied by Imps, whose Confuse 16 is very dangerous. Imps have only 300 HP, but resist the three basic damage Elements. Scourge can work as an offense, but physical attacks are better—unless they cast Blink, at least.
Bombs have a lot of HP and are highly likely to Self-Destruct, but this attack is entirely negated if used on a Character with at least 40 Defense. At this point, the Bombs may actually be one of the more relieving encounters to contend with. They rarely come accompanied by a Hill Gigas, who usually represents more of a threat. Ghosts are spellcasting Undead who can cast Stun 16 and Scourge 16 on individual Characters, making both quite powerful. They can also blunt your counterattacks with Curse and Mini. Fortunately they have the usual Undead weaknesses to Fire and Cure and a relatively manageable 540 HP and 35 Defense.
The final common encounter is with one or two Big Horns, the boss of the Tropical Island, and up to two Flying Rays. Big Horns remain tough foes, with a bunch of strong attacks and over 1,000 HP. Flying Rays have fewer HP, but even more attacks. They are Magic Beasts and thus will take extra damage from the Wing Sword and Demon Spear, but with these HP totals, this is likely going to be a long fight. Spells like Blink and Berserk can help speed it up.
The rarer encounters feature even more Monsters of note. Vampire Girls are relatively easy to kill Undead with 540 HP, but their five HP draining attacks can cause problems for any front-line fighter with low Evasion. No amount of Defense will stop the drain effect. They can also use Charm 6 on the party. They are sometimes accompanied by the Killer Mantises you saw in the Castle Fynn Basement. As with there, Ice is your most effective weapon against them.
Finally, the rarest encounter in the area is against the latest new type of slime, Black Flans. Fire is your only option here, though fortunately they aren't much of a threat. Their four attacks cause Poison but aren't otherwise a big deal. They sometimes come along with Red Mousses, who don't resist Fire but who need Lightning to reliably take them out. You may also see Red Souls with them, who remain annoying since they absorb every Element. You can cut through their 540 HP much more quickly with physical attacks than was the case back in Kashuan Keep, but they're likely to get off a few level-8 Elemental attack spells regardless.
The Eastern Approach
A much safer way to reach Mysidia is to sail your ship southwest from Altair, landing it at the southernmost point you can reach. You'll have to briefly head east around some mountains, but then follow the southern mountain range west to Mysidia. The Random Encounters you'll run into are much tamer than those Near the Mysidian Tower, though still dangerous.
The most common foes here are Black Flans, sometimes accompanied by Red Mousses but never by Red Souls. They shouldn't pose much of a problem, though they will be a drain on your MP. Once again, you'll see a lot of Bombs, sometimes with the weaker Mines in tow.
The final common encounter is with a group of Cockatrices. They won't go down in one hit like those in FFI, and their four attacks can turn your Characters to Stone. Having your Esuna Spell at at least level 5 is a good idea at this point in the game. The Wing Sword or Demon Spear is particularly effective against these Magic Beasts.
The uncommon encounter with Brains is nothing new, and they remain a threat to inflict Amnesia. Groups of Specters, Ghasts, Revenants, and Wraiths should be trivial to take out by this point in the game. Malboros make their first appearance here, though not in quite the form series veterans might expect. They have five attacks that can cause Paralysis, and are vulnerable to Lightning. With 750 HP, they're much hardier than the Parasites that sometimes accompany them. Last but not least, the rarest encounter in the Mysidia Area is with a Behemoth, just like the one you fought in the Coliseum.
The Western Approach
The closest you can land your ship to Mysidia is actually to the west of the town. Unfortunately, this is a long sailing trip from just about anywhere. Ocean encounters should be no threat, so this is still the safest way to go. The best landing point can be found by following the coastline west after passing through the strait to the outer sea (or heading northwest from the Tropical Island). There is a narrow inlet, and you can disembark there and make a short walk east.
You'll most likely only fight Monsters from the Mysidia Area on this trip, but head too far west and you'll have slightly different encounters. Groups of 1–3 Killer Mantises are common, while Cockatrices are a bit rarer. Malboros won't appear at all here, and Behemoths remain the rare encounter.
Your main task here is to visit the small cave in the southern part of town and put the White Mask on the statue within. You can also visit an unmarked building in the southwest and "speak" to the bookcase to learn interesting facts about various Keywords. Your next stop is the Mysidian Cave, which is a bit of a walk, but you can easily afford to carry Cottages (and likely have found a few recently), so you shouldn't need to come back here to rest.
Mysidia
Mysidia is the town of magic, and as such, almost every Spell you can buy is sold here. (The only exception are the white magic Spells sold in Fynn.) Four of them are newly available. Holy is the sole white magic damaging Spell, a non-Elemental Spell with a greater base power than Fire and its ilk. It's well worth learning and leveling so your white mage can contribute some damage when there is no obvious need for their other Spells. Swap can be used tactically to restore a white mage's MP, though be careful not to use it on a Monster with less! Once you find an Osmose Tome, you can Swap with your black mage to restore MP as well, allowing them to simply drain more. Swap is well-worth leveling to make it a more reliable Spell to use when needed.
The other two new Spells are defensive. Barrier grants the target Elemental resistances based on how many successes it gets. At first it can only resist Matter, which requires careful studying of ability lists to get much use out of, but at level 2 it can already resist Fire so it's not a bad Spell. Wall, on the other hand, will do absolutely nothing until you get it to at least level 5, because no Monster uses a Spell below that level. (On the other hand, you can exploit the Wall bug to kill any Monster in the game right up to and including the final boss, so there is that.)
Mysidia also sells Weapons and Armors. The Armor is all stuff you've seen before, but it's very nice to have it available for sale. Thief's Gloves and Giant's Gloves are both very nice, and you can use them to distribute stat bonuses to any characters who need them. The Knight's Armor is outclassed by the Gold Cuirass, but Ice Shields are good to have available.
The Weapons, in contrast, are all new. (You'll find all four in the next dungeon for free, but you probably have gil to spare at this point anyway.) The Power Staff is a nice upgrade if you have a front-line staff fighter. It has no special abilities and a relatively high magic penalty, so don't give it to an actual back-line mage. The Flame Lance is an upgrade over the Demon Spear (except against Magic Beasts, and its Fire-Elemental nature is good against a variety of Monsters, including Undead. The Ogrekiller is the first great axe you've seen in a while, and is extra effective against a series of future Giant bosses. Finally, the Ice Bow is a huge upgrade over the Flame Bow, though you may want to have both on hand to take advantage of their Elemental properties.
The only Shop in the game you haven't seen is found in the final dungeon, so feel free to splurge and buy anything that piques your interest in Mysidia. When there's nothing else to buy, premium Items like Elixirs will be more than happy to eat up your hard-won gil.
Shopping aside, remember you came to Mysidia for a reason. The townsfolk have a lot of information on the masks, the Crystal Rod, and the Mysidian Tower. You can find even more information on a variety of Keywords by checking the right-side bookshelf in the empty southwestern house. Your task right now is to find the stairs in the south part of town, and descend into the cave with the town statue. Use the White Mask on it to fulfill that part of your quest. You'll need to use the Black Mask in the Mysidian Cave. With both masks in place, you'll be able to find the Crystal Rod.
What your next task is depends on whether you found the Black Mask in the Tropical Island dungeon earlier. If so, just head to the Mysidian Cave. Otherwise, check the Tropical Island chapter of the Walkthrough. All of the Monsters in the Tropical Island should be trivially easy at this point—the final boss is literally a Random Encounter you might have already fought on the World Map—so this will be more time-consuming than difficult.