The annual pop culture event officially starts Thursday and runs through Sunday.
Hundreds of exhibitors and more than 130,000 guests are expected to pack the San Diego Convention Center for the sold out event.
Comics remain the foundation of the 40-year-old convention, but it has expanded to include movies, TV shows and video games.
The blogosphere is already abuzz about some of the offerings at this year's Comic-Con, where Hollywood continues to command a headlining presence.
This year, "Cowboys and Aliens" will hold its world premiere at the Comic-Con convention.
"Captain America" will play in San Diego for a full day before its nationwide opening Friday, and star Chris Evans is set to introduce the earliest screening.
Steven Spielberg and Peter Jackson are coming to the convention to talk about "The Adventures of Tin-Tin," Sony is offering a peek at "The Amazing Spider-Man," and the "Twilight" trio - Kristen Stewart, Taylor Lautner and Robert Pattinson - will again greet their fans at the Con.
The Associated Press contributed to this story.