The Marvel Cinematic Universe may have grown massively once the Multiverse was created in the Season 1 finale of Loki. However, this wasn't the true beginning of the MCU's growth. In fact, that came in Doctor Strange with the acknowledgment of other realms and dimensions. Since then, audiences have been made aware of the many threats these locations provide and the benefits. But things have definitely gotten out of hand as new enemies begin to emerge.
Kang the Conqueror has become a prominent threat in the MCU as the heroes will have to fight against not one Kang but a Multiverse of variants. As a result, the endless possibilities always mentioned have become a prominent and dangerous reality. But even still, there's potential for greater threats that could directly endanger the universe in a way none could expect -- namely, the Negative Zone. However, it couldn't have happened without the actions of Doctor Strange and Loki.
How Did Loki and Doctor Strange Create the Negative Zone?
In the comics, the Negative Zone was a reality made up of anti-matter that would kill most organic life instantly. However, insectoid creatures have survived, led by their ruler, Annihilus, and remain in survival mode as the zone begins to implode on itself. As a result, it is much older than Earth-616's reality. While it was discovered by the Fantastic Four in the comics, it still hasn't been introduced in the MCU. But with Doctor Strange confirming the existence of various dimensions and realms, it's possible the Negative Zone was one of them. This could've become even more possible with the creation of the Multiverse, turning the zone into a different reality of anti-matter rather than a different dimension.
Since it hasn't been found in the MCU, it could be the perfect opportunity to set up an Ultron-level threat as discovered by the Fantastic Four. With Loki and Doctor Strange visiting these realities, it's possible Reed Richards could've added science to the magic, creating the first multidimensional portal. As a result, he could inadvertently open a portal to the realm. Being natural explorers, the team would enter it and begin meddling, giving Annihilus and his army a taste of a reality that wasn't dying but rich with food and shelter. Therefore, it could create a danger that could lead to another major crossover event called Annihilation.
What Could This Realm Offer the MCU?
The Negative Zone may be a place where everything is on borrowed time, and its inhabitants have become ruthless survivors that live to feed and destroy, but that doesn't mean it has no value. In fact, the debut of Annihilus and his race would create a villain with a motivation none have had before him to live. Because of this, when the door is opened, and Annihilus is given a chance to lead his armies to a new land, it could lead to devastation. In the comics event known as Annihilation, the cosmic side of Marvel must contend with a force known as the Annihilation Wave that acts like cosmic locusts, nearly destroying the Nova Corps and consuming long-standing planets. Currently, the cosmic MCU hasn't had a major event but is primed for one. Therefore, the Annihilation Wave could be a force to deal with.
It was exciting and fresh when Doctor Strange introduced viewers to other dimensions. However, when Loki introduced the Multiverse, there was a sense of fear of the unknown. But those feelings would evolve into dread, leading to the Negative Zone. By teasing Annihilus and the Annihilation Wave, a realm of possibility would instead be a Lovecraftian horror story where creatures of nightmare would exist solely to destroy reality in a primal way. It's scary and something the MCU has never faced before. To make matters worse, it would've been a team effort by some of the most powerful minds in the MCU.