This paper adopts the analytical insights of Neoclassical Realism to examine why Cambodia enhances its political and security cooperation with China in the Belt and Road Initiative (BRI), what are the determining factors to this cooperation, what are their implications and challenges; and how are these challenges being managed. This is because Neoclassical Realism is able to explain “variation in the foreign policies of the same state over time or across different states facing similar constraints” (Taliafferro et al., 2009). It also explains “political phenomenon ranging from short-term decision-making, foreign policy behaviour, and pattern of grand strategic adjustment of individual state, to systemic outcomes, and ultimately to the evolution of that international system itself” (Ripsman et al., 2016). Accordingly, this paper discusses the following themes. One, Cambodia-China’s political and security cooperation in the BRI era. Two, their major determinants. Three, their implications and challenges. Four, the conclusion.