Mitochondrial adaptations to various environmental cues contribute to cellular and organismal adaptations across multiple model organisms. Due to increased complexity, a direct connection between mitochondrial integrity and oxygen fluctuations, and survival fitness was not demonstrated. Here, using C. elegans as a model system, we studied the role of HIF-1, Hsp90, and TRAP-1 in mitochondrial adaptations during chemical hypoxia. We show that Hsp90 (Hsp90 mutant) but not HIF-1 (HIF-1 mutant) affects hypoxia adaptation in nematodes. TRAP-1 (TRAP-1 knockdown) interfered with the survival and fecundity of worms. Compared to Hsp90, TRAP-1 has induced a significant decrease in mitochondrial integrity and oxygen consumption rate. The complex I inhibitor rotenone did not affect ATP levels in Hsp90 worms. However, ATP levels were decreased in TRAP-1 worms under similar conditions. The glucose restriction has reduced, and glucose supplementation has increased the survival rate in Hsp90 worms. Neither glucose restriction nor glucose supplementation has significantly affected the survival of TRAP-1 worms in response to hypoxia. However, TRAP-1 inhibition using a nanocarrier drug has dramatically reduced the survival rate in response to hypoxia. Our results suggest that Hsp90 and TRAP-1 independently regulate hypoxia adaptations and metabolic plasticity in C. elegans. Considering the emerging roles of TRAP-1 in altered energy metabolism and cellular adaptations, our findings gain importance.