The subject of pre-earthquake ionospheric signatures has always been contentious and debatable. Some of the previous reports have documented unforeseen and unusual variations in some of the atmospheric and ionospheric parameters well before an earthquake. Here, we analyze the ionospheric response to Nepal Gorkha Earthquake of April 2015 from the Indian subcontinent, which was one of the most powerful and disastrous natural calamity in past ~80 years over the Himalayan region. Killing nearly ~9000 people and more than ~20000 people injured with property damage of the order of several billion dollars. In view of sever earthquakes occurrences, their prior information on the short time scale is warranted for mitigation of associated disaster. We report for the first time, a case which shows a strong link in anomalous variations between VLF sub-ionospheric signal and mesospheric ozone one day prior to both main April 25, 2015 (Mw= 7.8) earthquake and its biggest aftershock on May 12, 2015 (Mw=7.3). Observations depict an unusual variation in VLF signals amplitude and shift in terminator time (TT) strongly linked with enhanced (depleted) mesospheric ozone variation in upper (lower) D-region altitudes prior to the earthquake. This eventually led to increases in D-region ionospheric electron density. It is surmised that simultaneous continuous observations of both VLF waves and mesospheric ozone can be considered as an important tool to identify the prior earthquake signatures in the vicinity of the extremely earthquake-prone zone such as Himalayan region. In this context, the current report opens up a new dimension in lithosphere-atmosphere-ionosphere coupling during the earthquake preparation processes itself.