A pituitary adenoma (PA) is a common intracranial neoplasm, and is a complex, chronic, and whole-body disease with multicausing factors, multiprocesses, and multiconsequences. It is very difficult to clarify molecular mechanism and treat PAs from the single-factor strategy model. The rapid development of multiomics and systems biology changed the paradigms from a traditional single-factor strategy to a multiparameter systematic strategy for effective management of PAs.A series of molecular alterations at the genome, transcriptome, proteome, peptidome, metabolome, and radiome levels are involved in pituitary tumorigenesis, and mutually associate into a complex molecular network system. Also, the center of multiomics is moving from structural genomics to phenomics, including proteomics and metabolomics in the medical sciences. Mass spectrometry (MS) has been extensively used in phenomics studies of human PAs to clarify molecular mechanisms, and to discover biomarkers and therapeutic targets/drugs. MS-based