Gru, a supervillain living in a quiet suburban neighborhood, prides himself on being the most notorious criminal mastermind. With an army of loyal, yet mischievous yellow minions and an elderly scientist named Dr. Nefario, Gru orchestrates grandiose heists, the latest of which is to shrink and steal the moon. Driven by a desire to assert his superiority and fueled by personal childhood disappointments, Gru is determined to pull off this feat to secure his legacy as the greatest villain of all time. His plans, however, are interrupted when a young rival villain, Vector, outshines him by stealing the Great Pyramid of Giza, stoking Gru's competitive spirit.

Gru's mission to reclaim his top spot leads him to adopt three orphaned sisters: Margo, Edith, and Agnes. Their initial purpose is to infiltrate Vector's heavily defended compound as cookie-selling girls scouts. Over time, the girls begin to see beyond Gru's cold and ambitious exterior. They grow on him and, against his former judgment and intentions, they start to bond, turning Gru's life upside-down. As Gru spends more time with his adoptive daughters, his villainous persona and grand schemes come into conflict with the burgeoning paternal emotions he feels, leading him to question his own identity and priorities.