The Goo Blob is one of the nastiest monster types, crippling anyone who does not have a way to deal magic damage or pierce physical resists. For the vast majority of characters, the only effective way to attack a Goo Blob is with the BURNDAYRAZ glyph, which can be problematic if you have not yet located it. Even once you have the glyph, most characters are only capable of using it twice in succession, which is seldom enough to kill a challenging Goo Blob on its own.
There are a few other ways to deal with resistances. Both Jehora Jeheyu and Binlor Ironshield offer ways to erode monster resistances, the BYSSEPS glyph can be used to whittle down physical resists as well, and the Really Big Sword is a superb item for this purpose, but all of these have limitations. Jehora's chaos avatar boon is expensive and non-repeatable, and Binlor requires you to have already revealed the target monster making it impossible to use it proactively. The BYSSEPS glyph is time consuming and often impractical, and the Really Big Sword is a pain to carry around for an entire dungeon run just to deal with a few physical resist monsters.
Often the best way to deal with a goo blob is to fireball it twice, kill a weaker monster to level up, then hit it with two more fireballs. This will usually leave it sufficiently weakened for you to completely dispatch it. Aside from the unique case of the Half-Dragon, only specialized spellcasting characters with lots of mana will have an easy time with Goo Blobs.
The Goo Blob boss has a whopping 75% physical resistance. Everything that goes for the regular goo blob goes double for him, but because you can afford to put more resources into fighting a boss than a regular monster you often have more leeway to use normally difficult approaches. The Glowing Guardian cleansing boon in particular, which is normally much too expensive to use on regular monsters, works fabulously against this boss.