Environment pollutants are acting like invisible killers in today’s world as the inhalation of colorless, odorless and toxic gases causes serious health issues and even leads to death. Gas sensors are therefore widely researched and developed to detect and quantify the concentration of target gases for healthcare applications. Considering the potential of gas sensors, this chapter presents the timely evolution of gas sensors, focusing on the scientific and technological innovations over the past decades towards the exploration of wearable and self-powered gas sensing applications. The contribution of nanotechnological advances in fundamental and applied research is reviewed, where the nanostructuring of materials mirrored the significant performance improvement in gas sensing field. Firstly, in this chapter, we summarize the recent advancements in wearable gas sensors and the use of different flexible substrates towards the development of wearable gas sensors is briefly discussed. Further, a look at the recent and ongoing efforts made by the researchers towards the development of next-generation gas sensors is presented, emphasizing the paradigm shift of existing gas sensor technology using cutting-edge advancements in self-powered technology i.e., integration of triboelectric and piezoelectric nanogenerators with gas sensors. Finally, the future perspectives of self-powered gas sensors towards the sustainable and real-time environmental monitoring and human disease diagnostics are discussed.