Nanomaterials/or nanoparticles have been reported to influence human life in terms of their applications in the food, drugs, cosmetics, and pharmaceutical industries. Thus, humans are/will be exposed to nanomaterials via varying routes that may/may not induce toxic responses. Different routes of the same nanomaterials exposure can lead to diverse toxicity responses in humans. The inhalation exposure of copper nanoparticles has induced pulmonary inflammation in mice, whereas their oral administration has induced systemic toxicity to the kidneys, liver, and spleen in mice. Therefore, the toxicity evaluation induced by various nanomaterials’ routes exposure becomes compulsory before implementing nanomaterials based products. With this in mind, this chapter reviews the toxicity induced by various types of nanoparticles on the basis of their route of exposure.