Quantitative mass spectrometry (MS) continues to deepen our understanding of the immune system, quickly becoming the gold standard for obtaining high-throughput, quantitative data on biomolecules. The development of targeted and multiplexed assays for biomarker quantification makes MS an attractive tool both for diagnosing diseases and for quantifying the effects of immunotherapeutics. Because of its accuracy, the use of MS for identifying biomarkers of disease reduces the potential for misdiagnosis and overtreatment. Advances in workflows for sample processing have drastically reduced processing time and complexities due to sample preparation, making MS a more accessible technology. In this review, we present how recent developments in proteomics and metabolomics make MS an essential component of enhancing and monitoring the efficacy of immunotherapeutic treatments.