Parasitic nematodes of humans, animals and plants have a major adverse impact on global health and agricultural production worldwide. The ability of such worms to adapt to changing environments is essential for their survival inside and outside of hosts. Advanced nucleic acid sequencing and bioinformatic technologies have enabled an unprecedented number of worm genomes to be decoded, which is starting to improve our understanding of the parasites at the molecular level. However, there is still a lack of knowledge of host-parasite relationships and parasitism. Here, using Haemonchus contortus - one of the most important parasitic nematodes of livestock animals worldwide - as a model, we defined the somatic and excretory/secretory proteomes as well as the phosphoproteome and lipidome of this nematode to explore molecular alterations during its development via mass spectrometry-based tools. By integrating these -omic datasets, we have been able to elucidate adaptations, including nutrient acquisition and metabolism, that take place during this nematode’s transition from the free-living stage in the environment to the parasitic stage inside the host animal. Understanding how worms orchestrate the process of parasitism at the molecular level could assist significantly in the development of molecular intervention strategies against parasitic nematodes.