Human-Centered Epistemics introduces a framework for evaluating human systems against the structural constraints of reality rather than the narratives used to describe problems. The paper formalizes Harper’s Law, an invariant governing the relationship between human constructs and the reality substrate they operate within, and examines the systemic failures that emerge when problem narratives are treated as primary design inputs. Drawing on observations across organizational systems, computational architecture, and epistemic methodology, the work develops a substrate-first approach to system design intended to reduce structural debt, coordination overhead, and systemic friction. The paper also introduces early computational validation through the Harper Engine, a prototype architecture demonstrating measurable performance advantages when substrate alignment is treated as the governing design principle. Together, these elements outline the foundations of Human-Centered Epistemics as a formal field of inquiry and establish a research program for its continued empirical development.