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From the young age, Melina was involved with the Red Room Program, eventually doing four full tours of it. In 1993 she was assigned to an undercover operation to Ohio, where was part of the cover she lived with her "husband" Alexei, a Russian hero known as Red Guardian, and daughters Natasha and Yelena. Although their mission was a success and they were able to recover the data they were after, in 1996 their cover was blown and the "family" had to flee to Cuba. Melina was wounded in the escape and was separated from the others upon landing, while the girls were shipped back to Russia and put into the Red Room Program.[1]

Melina came to work for General Dreykov, developing a system for chemical control over a subject's actions, to the point where they could be ordered to stop breathing or otherwise kill themselves. This new method of obedience replaced the previous psychological conditioning in the newer generation of Red Room graduates, while Melina continued her work on perfecting and refining it.[1]

In 2016 an antidote that could instantly break the chemical conditioning was developed. Dreykov sent several Widows after it, but Yelena became doused with it and went on the run with the rest of the samples. She brought in Natasha, and together they broke Alexei out of the Siberian prison. He in turn led them to Melina, resulting in their "family" reuniting for the first time in 20 years. Natasha convinced Melina to help them bring down Dreykov, but Yelena and Alexei had to be kept in the dark for their plan to work.[1]

Melina informed the Red Room, and the enemies of Dreykov were captured and taken to the floating Academy that served as his headquarters. Melina's knowledge of the facility enabled Yelena to escape, recover the antidote samples that were captured alongside them and release it into the group of Black Widows, instantly snapping them out of Dreykov's control. Melina had destabilized one of the structure's engines, and everyone was forced to make a frantic escape in which Dreykov was killed for good. After landing safely, Natasha said goodbye to her family and tasked Melina with replicating the antidote, so that the rest of the Widows across the world could be freed as well.[1]

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