Hypoxia is a salient feature observed in most solid malignancies that holds a pivotal role in angiogenesis, metastasis and resistance to conventional cancer therapeutic approaches, and thus enables cancer progression. However, the typical characteristics of hypoxic cells such as low oxygen levels and highly bio-reductive environment can offer stimuli-responsive drug release to aid in tumor-specific chemo, radio, photodyanamic and sonodynamic therapies. This approach based on targeting the poorly oxygenated tumor habitats offers the prospective to overcome the difficulties that arises due to heterogenic nature of tumor and could be possibly used in the design of diagnostic as well as therapeutic nanocarriers for targeting various types of solid cancers. Consequently, hypoxia triggered nanoparticle based drug delivery systems is a rapidly progressing research area in developing effective strategies to combat drug-resistance in solid tumors. The present review presents the recent advances in the development of hypoxia-responsive nanovehicles for drug delivery to heterogeneous tumors. The initial sections of the article provides insights into the development of hypoxia in growing cancer and its role in disease progression. The current limitations and the future prospective of hypoxia-stimulated nanomachines for cancer treatment are also discussed.