The evidence-based treatment (EBT) movement has primarily focused on core intervention content or treatment fidelity and has largely ignored practitioner skills to manage interpersonal process issues that emerge during treatment, especially with difficult-to-treat adolescents (delinquent, substance-using, medical non-adherence) and those of color. A chief complaint of “real world” practitioners about manualized treatments is the lack of correspondence between following a manual and managing microsocial interpersonal processes (e.g. negative affect) that arise in treating “real world clients.” Although family-based EBTs share core similarities (e.g. focus on family interactions, emphasis on practitioner engagement, family involvement), most of these treatments do not have an evidence base regarding common implementation and treatment process problems that practitioners experience in delivering particular models, especially in mid-treatment when demands on families to change their behavior is greatest in treatment – a lack that characterizes the field as a whole. Failure to effectively address common interpersonal processes with difficult-to-treat families likely undermines treatment fidelity and sustained use of EBTs, treatment outcome, and contributes to treatment dropout and treatment nonadherence. Recent advancements in wearables, sensing technologies, multivariate time-series analyses, and machine learning allow scientists to make significant advancements in the study of psychotherapy processes by looking “under the skin” of the provider–client interpersonal interactions that define therapeutic alliance, empathy, and empathic accuracy, along with the predictive validity of these therapy processes (therapeutic alliance, therapist empathy) to treatment outcome. Moreover, assessment of these processes can be extended to develop procedures for training providers to manage difficult interpersonal processes while maintaining a physiological profile that is consistent with astute skills in psychotherapeutic processes. This paper argues for opening the “black box” of therapy to advance the science of evidence-based psychotherapy by examining the clinical interior of evidence-based treatments to develop the next generation of audit- and feedback- (i.e., systemic review of professional performance) supervision systems.