Mass spectrometry (MS)-based metabolomics is one approach used to investigate the metabolic profiles of cancer cells. To gain a comprehensive interpretation of the metabolite variation profiles in biological systems, qualitative and quantitative information is required. This typically involves a discovery-driven untargeted profiling analysis using a high resolution accurate mass (HRAM) MS platform followed by a hypothesis-driven targeted analysis using a tandem triple quadrupole MS platform. Here, we propose a metabolomics research paradigm shift which utilizes a hybrid quadrupole-Orbitrap mass spectrometer to achieve an integrative approach of these two methodologies. The discovery and targeted workflows to study the metabolic profiles of Panc-1 cancer cells will be discussed.