This paper identifies and compares three existing systems of innovation approaches, namely, the national system of innovation approach, the technological/sectoral system of innovation approach, and the regional system of innovation approach. By focusing the analysis on knowledge, the research scope, unit of analysis, and analytical frameworks applied by each approach are analyzed and synthesized. The paper reveals that the three approaches claim their major knowledge links, facilitating factors, and boundaries differently. Although three methods have emerged in mapping systems of innovation, these methods provide complementary views, rather than substitutive ones, for constructing a complete configuration of an innovation system. Four methodological problems exist: inconsistent definition of innovation, top-down orientation, independence among innovation systems, and ex-post qualitative analysis. Finally, further methodological issues regarding systems of innovation studies are suggested.