The film's plot has Sherlock Holmes and Dr. Watson attempting to recover a stolen necklace, formerly worn by Cleopatra, from Professor Moriarty. Holmes tries to convince the police that the professor is a criminal, but they are disbelieving.
In World War II, a British secret agent carrying a vitally important document is kidnapped en route to Washington. The British government calls on Sherlock Holmes to recover it.
Unable to process the death of his daughter, Detective Boyd embarks on a hunt for a serial killer who murders according to a brutal tribal ritual: Muti. The only person who can help Boyd is Professor Mackles, an anthropologist who hides an unspeakable secret. The line between sanity and madness thins as Boyd goes deeper into the killer’s world.
Sherlock Holmes is drawn into the case of Jack the Ripper, who is killing prostitutes in London's East End. Assisted by Dr. Watson, and using information provided by a renowned psychic, Robert Lees, Holmes finds that the murders may have their roots in a Royal indiscretion and that a cover-up is being managed by politicians at the highest level, all of whom happen to be Masons.
Holmes and Watson board a passenger train bound from London to Edinburgh, to guard the Star of Rhodesia, an enormous diamond worth a fortune belonging to an elderly woman of wealth; but within the first hour of the trip, the woman's son is murdered and the diamond stolen and any of the passengers in their car could be the killer thief.
During WWII several murders occur at a convalescent home where Dr. Watson has volunteered his services. He summons Holmes for help and the master detective proceeds to solve the crime from a long list of suspects including the owners of the home, the staff and the patients recovering there.