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Resistance to change remains central to psychoanalytic practice: Patients often maintain dysfunctional beliefs and relational patterns even when they recognize their destructive nature. While psychoanalysis has richly described resistance as a defense against painful affect and threats to internal object relations, the process-level dynamics through which resistance persists over time have remained incompletely articulated. This article proposes a neuropsychoanalytic model that conceptualizes resistance in terms of two interconnected regulatory constraints: defensive resistance arising through affective gating and structural resistance rooted in the inertia of deeply entrenched beliefs. Integrating psychoanalytic formulations of affect tolerance and working through with principles of predictive processing, the model clarifies why therapeutic transformation often proceeds in oscillating cycles and what conditions enable patients to bear the affective intensity required for change. By linking clinical observation with process-level accounts of mind–brain functioning, the framework seeks to deepen psychoanalytic understanding of resistance and therapeutic transformation while fostering dialogue with contemporary neuroscience.