- "Your mother saved thousands of lives that day, knowing she'd be lost in the Quantum Realm. Alone. Afraid. Gone forever. Telling you that she wasn't coming home, was the hardest thing that I ever had to do. But then Scott showed up… or should I say, broke into our house. And when he went to the Quantum Realm... he came back, everything changed. I started to wonder… could your mother still be alive?"
- ―Hank Pym to Hope van Dyne
During a mission for S.H.I.E.L.D. with her husband Hank Pym, Janet van Dyne, operating as the Wasp, used the capabilities of her Wasp Suit to shrink to an atomic level in order to stop a missile. Although van Dyne successfully destroyed the rocket, this caused her to fall into the Quantum Realm, where she was trapped for decades. Both Pym and their daughter thought that van Dyne was dead. However, when Scott Lang was in turn trapped in the Quantum Realm but managed to return, Pym began hoping that van Dyne was still alive and that he could rescue her.
Two years later, following the Clash of the Avengers, Lang received an apparent message from van Dyne in the form a shared memory of her daughter, which allowed Pym and Hope to confirm their suspicions about van Dyne being alive. They briefly opened a tunnel to the Quantum Realm, however, it was only able to be open for a few seconds. Later, when able to open a more stable tunnel, van Dyne, sending a message through Lang, gave her exact location, before revealing that there were only two hours before the Quantum Realm's instability would move her, causing her to disappear for another century.
Just before going through with the rescue, Hank Pym told Scott Lang and Hope van Dyne that he would be the one to enter the Quantum Realm, allowing Scott and Hope to distract Ghost away from the lab, in an effort to have a safe rescue. With the battle for the laboratory ongoing, Hank entered the Quantum Realm with just about fifteen minutes left before Janet's location would change. Upon arriving at Janet's location however, Pym becomes disoriented due to the Quantum Realm's nature, but Janet is able to find him and they reunite. They then come back with the lab returning to its original size.
Immediately following her escape from the Quantum Realm, Janet van Dyne encountered Ghost, who had planned to extract quantum energy from her in order to cure her condition of quantum instability. Using the powers she had obtained through her long stay in the Quantum Realm, van Dyne transferred a significant amount of quantum energy into Ghost, thus temporarily stabilizing her condition and ending Ghost's campaign against Ant-Man and his allies.
However, van Dyne did not have much time to enjoy her time out of the Quantum Realm. Indeed, while she oversaw an expedition of Ant-Man into the Quantum Realm so that he could harvest more quantum energy for Ghost, van Dyne was disintegrated along with Hank Pym and their daughter Hope due to Thanos activating the Infinity Gauntlet and initiating his universal genocide.