<p>The integration of <i>nomothetic</i> (generalist) and <i>idiographic</i> (specialist/localized) approaches in knowledge production represents a crucial endeavor, particularly within the realms of ethnography and ethnology. Despite this, enduring skepticism stemming from contemporary anthropological perspectives influenced by postmodernism persists regarding the utility of nomothetic propositions. Historically, cultural materialism has advocated for a generalist approach to understanding human cognition, behavior, society, and culture, yet faced application challenges in light of empirical evidence highlighting the dual influence of both material conditions and ideational factors on human behavior. Karl Popper's three-worlds model offers a recursive mechanism for sociocultural transformation, bridging the gap between materialist and ideational perspectives. Using Popper’s model, we propose a synthesis between materialism and mentalism, which we call <i>Semio-Materialism</i>. By combining anthropological semiotics, cultural materialism, and a sensitivity to cybernetic advancements, this paper promotes an interdisciplinary dialogue that accommodates various theoretical frameworks, thereby advancing theory-building in anthropology.</p>