Buckaroo Banzai, a multi-talented physicist, neurosurgeon, and rock musician, successfully tests his new invention, the Oscillation Overthruster, which allows him to travel through solid matter by accessing the 8th Dimension. During the test, Buckaroo inadvertently releases a malevolent alien entity named Dr. Emilio Lizardo, who had been trapped in the dimension years earlier. Lizardo, also known as Lord John Whorfin, seeks to free other Red Lectroids, his alien comrades imprisoned in the 8th Dimension. Now, with the help of his eclectic team, the Hong Kong Cavaliers, Buckaroo must prevent these aliens from taking over Earth.

As Buckaroo makes strides to thwart the alien invasion, he encounters Penny Priddy, a woman who bears a striking resemblance to his deceased wife and gets entangled in his mission. Complications arise when the President of the United States and other government agencies get involved, revealing a clandestine network of alien alliances and enemies on Earth. With time running out and betrayal lurking at every corner, Buckaroo and his allies must devise a daring plan to stop Whorfin and the Red Lectroids from launching an interdimensional assault.