In March 1975, a Sino-Soviet border conflict escalates into full-scale war in which biological warfare destroys most of the human race.

Struggling to maintain his sanity, he spends his days patrolling the now-desolate Los Angeles, hunting and killing members of "the Family", a cult of plague victims who were turned into homicidal nocturnal albino mutants.

Through flashbacks, Neville remembers how martial law was imposed and the majority of people who succumbed to the plague were killed instantly by asphyxiation.

At night, living atop a fortified apartment building equipped with an arsenal of weaponry, Neville is a prisoner in his own home.

The Family's attempts to extract Neville from his residence have failed, due in part to their insistence on using archaic weaponry and siege warfare.

Neville is sentenced to death and nearly burned at the stake tied to a large wooden wheel representing modern technology in Dodger Stadium.

Neville realizes salvaging humanity would take years as he will need a long time to duplicate the original vaccine.

The Family then attacks, sending Matthias' second-in-command, Brother Zachary, to climb up the outside of Neville's building to the open balcony of his apartment.

Matthias, who finally has the upper hand, forces Neville to watch as the Family sets his home and equipment on fire.

[10] Despite careful planning by the film crew, some exterior shots captured bystanders and moving cars in the background of some scenes.

[14][15] Screenwriter Joyce H. Corrington stated that in developing the script for The Omega Man, the character of Lisa, played by Rosalind Cash, was created due to the rise of the Black Power movement, which was particularly prominent in American culture at the time the film was made.

Heston wrote in his autobiography that The Omega Man was Cash's first leading role in a film, and that she was understandably "a little edgy" about doing a love scene with him.

Heston explained, "It was in the seventies that I realized a generation of actors had grown up who saw me in terms of the iconic roles they remembered from their childhoods.

[18] Howard Thompson gave a mostly negative review in The New York Times, saying, "the climax is as florid and phony as it can be,"[19] while A.D. Murphy of Variety described the film as "an extremely literate science-fiction drama.

"[20] Gene Siskel of the Chicago Tribune gave the film one star out of four, writing that director Boris Sagal "must have resembled a juggler trying to keep four dramatic balls aloft.

"[21] Kevin Thomas of the Los Angeles Times wrote that the film was "strictly a potboiler, but it's without pretensions and never runs dry.

"[22] Tom Shales of The Washington Post wrote, "Director Sagal displays no great affinity for science fiction — he's from TV land — but he generally upholds interest and can certainly handle the shocks and suspense, which are both abundant and enjoyable in a Saturday matinee way.

"[23] Director Tim Burton said in an interview for his 2009 Museum of Modern Art exhibit, "If I was alone on a desert island, I'd probably pick something that I could relate to—probably The Omega Man with Charlton Heston.

"[24] In another interview, with the Australian Centre for the Moving Image, Burton remarked that no matter how many times he has seen it, if it is on television, he will stop to watch it.