We’ve long viewed neurological injuries as a black box. Our treatment outcome assessments are often binary, overlooking the many pathogenic mechanisms and their modulators that influence results, such as genetic factors, age, and comorbidities. Even for a given drug, there are numerous variables to consider, including pharmacodynamic specificity, dose, timing, and the effectiveness of the delivery method. This complexity creates a “complex problem mess” that is daunting and intriguing for research. It’s time to develop strategies to track the evolution of neuropathology, ensure drug delivery, and assess the treatment’s impact on the specific injury pathway rather than the net outcome of injury. This chapter describes how we could treat complex neurological diseases by delving into the black box of pathology by using specific injury-guided arterial interventions.