According to the Significance Quest Theory (Kruglanski et al., 2009) and the 3N model (Webber & Kruglanski, 2018), violent extremism is the product of a quest for significance triggered by a need for significance (need) and nourished by subscription to a radical ideology (narrative) and affiliation with a radical network (network). The present systematic review aims to synthesize extant quantitative empirical research mobilizing this framework. We screened a total of 151 reports, of which 31 met our eligibility criteria. These regrouped a total of 84 studies. Our findings show an important heterogeneity in the measurements and manipulations of significance (need and quest), narrative, and network, as well as in the pathways examined. Moreover, while the theory’s predictions are confirmed by a majority of the studies’ findings (n = 74), such predictions are also infirmed by a considerable number of studies’ findings (n = 29). This is particularly the case for the empirical evidence related to the association between significance loss and extremism, as well as the association between significance loss and narrative, and between network and extremism. More consistent evidence was found concerning the association between significance loss and network, significance quest and narrative, significance quest and extremism, and narrative and extremism. The methodological, operational, and theoretical implications of these findings are discussed.