In response to shortcomings of the current classification system in translating discoveries from basic science to clinical applications, NIMH offers a new framework for studying mental health disorders called Research Domain Criteria (RDoC). This framework holds a multidimensional outlook on psychopathologies focusing on functional domains of behavior and their implementing neural circuits. In parallel, the Predictive Processing (PP) framework stands as a leading theory of human brain function, offering a unified explanation for various types of information processing in the brain. While both frameworks share an interest in studying psychopathologies based on pathophysiology, their integration still needs to be explored. Here, we argued in favor of the explanatory power of PP to be a groundwork for the RDoC matrix in validating its constructs, creating testable hypotheses about mechanistic interactions between molecular biomarkers and clinical traits, and finally, considering developmental trajectories and environmental factors in psychopathologies. Together, predictive processing may serve as a foundation for achieving the goals of the RDoC framework.