Recent advances in metabolomics are accelerating natural product (NP) drug discovery. NPs possess diverse biological relevance and comprise a significant portion of our modern pharmacopeia. We highlight studies from the past two years with innovative discovery techniques, ranging from small sample analyses to large-scale data-driven approaches. We focus on nuclear magnetic resonance- and mass spectrometry-based metabolomics for their broad use and greatest advancements in the field. We highlight strategies that utilize computational tools to enable prioritization of samples based on structural novelty, cross-referencing structural data with bioactivity, and the development of innovative annotation techniques that surpass common library matching methods. We also look at the trajectory of metabolomic discovery of NPs over the last decade to inform how these platforms may further evolve. The goal is to enhance the likelihood and improve the efficiency of discovering NPs with pharmaceutical potential, while strategically harnessing data in order to reduce rediscovery and methodological redundancy.