The Pilot Research Project Core actively seeks, assesses, and supports novel and forward-thinking feasibility (pilot) studies within the UIUC Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling. Our Core and Center thrive when we facilitate the achievements of promising young investigators who are new to our 'omics measurement capabilities or addiction research, while also encouraging experienced researchers to extend their research to substance use/misuse and addiction. The selected pilot projects will have access to our considerable Center resources available through our scientific cores—Sampling and Separation, Molecular Profiling and Characterization, and Bioinformatics, Data Analytics and Predictive Modeling—to generate the data required for continued research and potential for longer-term support. The Pilot Research Project Core ensures that the NIDA / neuroscience research community continues to take advantage of the opportunities and expertise offered by our Center. Applicants who propose feasibility studies, who want to explore how to incorporate ‘omics data into their research, or what to start a new direction that fits the NIDA and Center research areas may qualify for support from the Pilot Core. To improve overall Center capabilities that will benefit multiple users, the Pilot Core will also support small technical, methodological, or conceptual developments from staff and users to improve Center measurement and informatics capabilities. Toward those goals, we outline three exemplary initial pilot projects targeting neuropeptides, transmitters, and proteins that are involved in multiple aspects of drug use. The first project aims to identify substrates of a receptor linked to addiction and neural plasticity. The second project focuses on characterizing neuropeptides to understand genetic factors contributing to oxycodone-related phenotypes and their role in opioid use disorder development. The third project aims to perform single-cell transcriptomics measurements for the project investigator, with the developed technology also benefiting other Center projects. We will solicit new proposals each year, and support up to eight additional projects for competitive review by the Core over the next five years. The Core has a rigorous process in place to solicit, assess, and select Pilot projects. Overall, the Pilot Research Project Core, an important component of the Center for Neuroproteomics and Neurometabolomics on Cell-Cell Signaling, encourages the use of cutting-edge technology, fosters cross-disciplinary collaboration, and accelerates progress in addiction research.