While looking for a way back to Earth, the Hulks discover the Leader stowed away on board the ship. Retribution must wait as the Agents of S.M.A.S.H. have to fight Ronan the Accuser and his Kree soldiers to save an old foe: Ego the Living Planet. But when Galactus comes to consume Ego the Living Planet, the Agents of S.M.A.S.H. must put themselves at risk to save the lives of their two enemies.
On Halloween, the Agents of S.M.A.S.H. encounter Nick Fury's Howling Commandos where they have been sent by Nick Fury to apprehend the Agents of S.M.A.S.H. The Howling Commandos have a change of plans when they end up helping the Agents of S.M.A.S.H. prevent Dormammu from breaking into Earth's dimension and turning all of humanity into Mindless Ones.
Upon being lured to an unnamed planet, the Agents of S.M.A.S.H. team up with their old friends the Guardians of the Galaxy to stop Super-Skrull and the Skrulls from using the Agents of S.M.A.S.H.'s gamma energy to create gamma-powered Skrulls in their latest plot to invade Earth.
The Agents of S.M.A.S.H. returns to Earth with Leader still in their possession even though they were blamed for the destruction of Vista Verde following the incident by Leader's Agents of C.R.A.S.H. They find Vista Verde under the rule of Abomination (who was pardoned and reinstated into the U.S. Army) upon learning this from Mayor Stan and finding Hulkbusters that are under his command. Now the Agents of S.M.A.S.H. must liberate Vista Verde and defeat Abomination before he can use one of Thunderbolt Ross' old weapons in his plan to attack other nations.
While being pursued by the military, the Agents of S.M.A.S.H. go after Leader when he steals all the confiscated weapons from their vault. When Devil Dinosaur is enlarged and let loose by Leader, the Agents of S.M.A.S.H. team up with Spider-Man to stop Devil Dinosaur and restore him to normal size.
Upon S.H.I.E.L.D. exonerating them from the frame-up in Vista Verde caused by the Agents of C.R.A.S.H., the Agents of S.M.A.S.H. track the Leader to a deserted island. They get stuck in a deadly maze (which Leader improved on Thunderbolt Ross' plans in his earlier fight with Hulk) where Hulk's rage is drained from him, making him mellowed out. After the rest of his teammates are captured, Hulk finds them in Leader's clutches at the center of the maze where Leader uses his machine to manifest Hulk's dark side in the physical form of Dark Hulk.
While saving Earth from a potentially catastrophic meteorite, the Hulks come face to face with a future version of Hulk called Maestro who might not be the hero they think he is. The rest of the Agents of S.M.A.S.H. are unaware of Maestro's true plans until they encounter a future A-Bomb.
Chasing Leader through time to World War II, Hulk teams up with a young Captain America to stop Red Skull who becomes Green Skull when enhanced with gamma energy by Leader. In the present, the Agents of S.M.A.S.H. team up with an old Captain America to fight and free the world from HYDRA which is led by Leader and operating a device that is powered by Green Skull.
A Kree armada led by the Supreme Intelligence who is invading in retaliation for Ronan the Accuser's incarceration. When the Kree free Ronan the Accuser and Leader, Hulk is torn between his two teams the Agents of S.M.A.S.H. and the Avengers where both groups fight to prevent the Kree from destroying Earth.