Alien invaders, referred to as "The Others," execute a series of catastrophic attacks on Earth dubbed "waves." The First Wave involves an electromagnetic pulse that disables all electronics and technology. The Second Wave sees the world's coastlines washed away by massive tsunamis, and the Third Wave unleashes a deadly pandemic that drastically reduces the human population. During these calamities, Cassie Sullivan, a determined teenage girl, struggles to survive and protect her younger brother, Sam. As society collapses and the fourth wave announces itself with the revelation that the aliens can inhabit human hosts, suspicion and paranoia reach their peak, tearing what's left of humanity apart.

Cassie finds herself on her own after being separated from her family and embarks on a perilous journey to rescue her brother, who has been taken by military forces promising safety. As she traverses an alien-dominated and devastated landscape, Cassie allies with a mysterious young man, Evan Walker, who harbors secrets of his own. Meanwhile, her brother is being trained with other children to become soldiers to fight against the supposed invaders. Uneasy alliances, the blur between friend and foe, and the resilience of the human spirit define Cassie's quest in a world marred by invasion and betrayal.