Filming took place in India, predominantly in Gujarat and Himachal Pradesh, in addition to Spain, Portugal, and Greece in Europe from February 2021 to March 2022.

[16] Ranganath Rao, an archaeologist and professor visits a library in Greece and through a book, written by Ptolemy, he discovers that Shri Krishna, before the end of Dvapara Yuga, entrusted his friend and counceller Uddhava with his anklet, which is equipped with all the solutions for deadly problems, humans are going to face in the succeeding Kali Yuga.

In Hyderabad, Karthikeya "Karthik", now a doctor who believes in science and logic is suspended for slapping a Mayor, who had attempted to perform a Yagna in the ICU for his son.

Considering all the inauspicious occurrences, Karthik's mother believes that her family is being punished for not being able to fulfil a vow made to Shri Krishna, a few years ago.

Karthik, Mugdha and Sadananda visit a sage to find about the man and learns that he belongs to the clan of Abheeras, an exiled community who resorted to dacoity but worshipped Shri Krishna.

Rao had found that the anklet was hidden by Uddhava, who left behind clues to reach it, as the right person is destined to get that.

Santanu, a professor in search of the anklet, kills Rao with evil intentions and was the one, responsible behind Karthik's arrest.

Karthik finds a peacock-shaped object in Krishna Thatakam and Mugdha decodes the Sanskrit inscription written on it, that leads them to Govardhan Hill.

Santanu apprehends the trio and leaves them in the desert to die but Mugdha arrives and rescues them, revealing that she had gone to her friend for finding about a person, who would help them in solving the mystery.

Together, the foursome leave to Himachal Pradesh for meeting a blind philosopher Dr. Dhanvantari, who explains that Rao and Santanu were a part of secret society, that believed that the ancient India is far more advanced in technology than the modern world.

Dhanvantari also explains that Krishna should be considered as a human rather than God, who was an extraordinary engineer for building his palace in midst of sea, a kinetic engineer for controlling Sudarshana Chakra, a doctor for knowing all the Ayurvedic treatment methods, a musician for being talented in playing flute, that helped as a music therapy and much more.

They manage to escape being drowned but are ambushed by an Abheera, who is forced to practice peace for 24 hours due to Krishna Paksha.

Karthik observes the constellations on a hill, the next clue led to through the telescope, they found and finds the final location.

Subsequently, Karthik embarks on a new mission to unfold the link between Krishna and deep waters of Atlantic Ocean.

[31][32] The post-theatrical digital streaming rights were acquired by ZEE5 and was premiered on 5 October 2022 (coinciding with Vijayadashami) in Telugu, Tamil and Hindi languages.

"[39] A reviewer for 123Telugu rated the film 3.25 out of 5 stars and noted, "Karthikeya 2 is a well made adventure thriller filled with great visuals and engaging narration".

"[44] A critic for Pinkvilla rated the film 3 out of 5 stars and said, "Karthikeya 2 executes quite a few dangerous events without building a proper context.

[3] Grace Cyril of India Today rated the film 1.5 out of 5 stars and wrote "Karthikeya 2 goes through various stages, but this journey could have been narrated in an easier manner.

[47] Writing for The Hindu, Sangeetha Devi Dundoo opined that the premise is reminiscent of Ashwin Sanghi's book The Krishna Key.