The restructuring of old industrial areas is one of the most important research topics in economic geography. In the macro context of the slowdown of globalization and the worldwide decrease of manufacturing production and demand, old industrial areas as typical problem regions have increasingly become a core target in national development strategies among many countries. Drawing upon an in-depth critical review of recent literature on the restructuring of old industrial areas in the past decade, this paper addresses the growing trend of variegated adoptions of paradigms in the research including four key approaches, namely, evolutionary economic geography, relational economic geography, institutional economic geography and geographical political economy. It also stresses that the gaps yet comparative merits in conceptual thinking, scale focus, tempo-spatial sensitivity and mechanism/process explanation among these paradigms have not generated enough intellectual interplays and complementation, but rather, have led to paradigmatic fragmentation and even repellence with each other. Despite the diversification in paradigmatic use for research, the increase of “fragmented” rather than “engaged pluralism” potentially hinders the explanatory power of existing theories and approaches in empirical research. In particular, we argue that evolutionary economic geography, arguably the most popular paradigm used in explaining and understanding the restructuring of old industrial areas, clearly suffers from a neglect of the role of multi-scalar and multi-actor agencies and a lack of multiple units of analysis in affecting the restructuring processes, mechanisms, outcomes and their geographies of old industrial areas. Given this, the paper integrates the multi-level perspective (MPL) in sustainability transition studies into the evolutionary economic geography approach. It builds up a multi-scalar analytical framework incorporating analyses of both downward and upward causation with different geographical scales, in which the interplay of micro-level change agency-based niche, meso-level regional path developmental regime and macro-level political-economic context landscape is positioned as the core for analyzing the restructuring of old industrial areas. This comprehensive multi-scalar framework is able to offer a better understanding of the restructuring of old industrial areas. Based on that, we further suggest several key orientations and agendas for future research on the topic.