The formerly modest, "geeky" gathering that began in 1970 has morphed into a sprawling, monstrous pop culture event attended by top talents from Hollywood, the gaming world and the publishing industry.
More than 130,000 fans are expected to congregate and join seemingly endless queues to take in Comic-Con's vast offerings — from sneak peeks of potential blockbuster movies, hotly anticipated video games and must-see TV to the latest in popular comics and rare, highly coveted collectibles.
There's a staggering amount of material on show, but here are 10 things we're looking forward to:
From the warm, positive fan reviews for TV's Supergirl at its eve-of-Comic-Con screening to fresh footage from the final Hunger Games and next Divergent movies, stories about strong women are a definite highlight. There's also the return of the popular Women Who Kick Ass panel (with Agent Carter's Hayley Atwell, American Horror Story's Kathy Bates and Game of Thrones' Gwendoline Christie among the participants).
Zombies, zombies, zombies
Lest you think that the undead wave is waning, Comic-Con has fresh meat planned: tasty tidbits from The Walking Dead and its upcoming spinoff Fear the Walking Dead, a reveal of zombie mode from the forthcoming Call of Duty: Black Ops 3 and a peek at the Pride and Prejudice and Zombies movie.
It's a Star Wars world
Really, any new detail about the Star Wars universe just about breaks the internet, so superfans are ready to pounce on any scrap of info or behind-the-scenes detail that Star Wars: The Force Awakens (aka Episode VII) director J.J. Abrams, writer Lawrence Kasdan and producer Kathleen Kennedy might unveil at the panel discussion.
Comic-Con wouldn't be Comic-Con without a plethora of superheroes. Canadian actor Ryan Reynolds cheekily reminded everyone his Deadpool character was San Diego-bound this week, but there's also keen interest in the Batman v Superman: Dawn of Justice panel, featuring director Zack Snyder and stars Ben Affleck, Henry Cavill, Jesse Eisenberg and Gal Gadot. Might we also get more from Fantastic 4 or X-Men: Apocalypse films as well?
Comics, the next generation
Comic giants Marvel and DC have been in the process of (once again?) rebooting, revamping, revitalizing and generally smashing up their respective universes, incorporating more diversity (in gender, ethnicity, sexuality, etc.) by recasting characters, rejigging storylines and enlisting fresh new creative voices. What will they unveil about this new generation of superheroes and villains?
The always entertaining Pulp Fiction and Django Unchained filmmaker is set to unveil new footage from his ensemble western The Hateful Eight, the project he once vowed to shelf after a script leak. He'll be joined by his star-studded cast, including Samuel L. Jackson, Kurt Russell, Jennifer Jason Leigh, Michael Madsen and Bruce Dern.
Computer screen to movie screen
The Warcraft movie is the latest example of a massively popular video game being translated into film form. Can filmmaker Duncan Jones really pull this off?
Former cult hit turned critical darling, Canadian series Orphan Black is returning to delight fans with a meet-up and panel in San Diego. The sci-fi show's Regina-born star Tatiana Maslany is slated to dish about what's next for her many characters.
We also proudly wave the Maple Leaf for the upcoming new web comedy Riftworld. Starring Being Erica's Erin Karpluk and Battlestar Galactica's Tahmoh Penikett, who's showing off the project in San Diego.
"I don't think he's going there expecting to outshine Ben Affleck and so on. He's just going out there and sharing what we have," Karpluk told CBC News of the web show, based on the short film The Portal which won accolades and a fan following at an earlier Comic-Con.
"We're not trying to save lives here: it's very entertaining."
Game of Thrones panel
The cast and creatives of the monster HBO hit are notoriously tight-lipped about what's to come in their adaptation of George R.R. Martin's blockbuster book series, but who knows. Fans might score a bit of news about the forthcoming sixth season. If not, everyone can simply wail and/or share a cathartic cry over the devastatingly bloody (and blockbuster) season five finale.
Surprises in store
What would Comic-Con be without surprise appearances, celebs and outrageous incidents (Hi Conan!)? We're staying tuned.