Giovanni leads Team Rocket, a criminal organization dedicated to seizing rare and powerful Pokémon to achieve global domination. His involvement intensifies directly within the Unova region during the Black and White series. Recognizing their successes against adversaries like Team Galactic, he promotes Jessie, James, and Meowth to Advanced Agent status, demonstrating heightened trust for critical missions.

He dispatches the trio to Unova with specific orders: destabilize the region and gather intelligence on rival group Team Plasma. Giovanni supplies resources but restricts their use of non-native Pokémon to maintain secrecy. Their initial assignments involve infiltrating Striaton City and harvesting Dream Energy, an experimental power source he aims to weaponize for Team Rocket's goals.

Giovanni later arrives in Unova personally to command Operation: Tempest, focused on capturing the Mythical Pokémon Meloetta. Utilizing specialized goggles created by Dr. Zager, he tracks the invisible Meloetta. After his Persian defeats Ash in battle, Giovanni traps Ash and Pikachu within a shrinking force field, threatening their lives to force Meloetta's surrender.

Securing Meloetta grants Giovanni access to the Abyssal Ruins. Using Meloetta's song, he summons the Reveal Glass, an artifact controlling the Legendary Pokémon Tornadus, Thundurus, and Landorus. Exposure to the Reveal Glass corrupts him, magnifying his darker impulses. He shifts focus from conquest to outright destruction, commanding the Legendary Pokémon to ravage Unova. This drastic change alarms his subordinates, as mass destruction deviates from Team Rocket's standard objectives. Jessie, James, and Meowth intervene, tackling him to disrupt the artifact's hold. Giovanni concedes the mission's failure and orders a withdrawal.

Following these events, Giovanni recalls the Pokémon the trio collected in Unova but permits them to continue operations in other regions. Team Rocket remains active under his ongoing oversight from a distance.