Co-injection molding and multi-cavity molding are common processes for plastic products manufacturing. These two systems are sometimes combined and applied in the manufacture of bifurcation-structure products. However, how the influential factors truly affect the core penetration behavior and the detailed mechanism of core penetration behavior has not yet been fully understood. In this study, it has focused on studying the multi-cavity co-injection system with a bifurcation runner structure. The results showed that when the skin-to-core ratio is fixed (say 72/28), the melt flow behavior of a co-injection system, utilizing the same material for both skin and core, is very similar to that of a single shot injection molding. Specifically, the non-symmetrical bifurcation runner structure will influence the flow behavior greatly and cause the core distribution imbalance between different cavities. However, it is observed that when the flow rate is increased, the core material will occupy more volume space in the upstream portion of the runner and the core penetration distance will be reduced in the flow direction downstream. This feature is very useful to further manipulate the skin/core interface in a multi-cavity system. Moreover, regarding how to improve a poor inter-cavity balance of core material distribution, using a suitable adjustment of the skin-to-core ratio will be greatly helpful. However, the core break-through defect can be a common problem in co-injection molding when an unsuitable skin-to-core ratio is used. To prevent the core break-through defect, increasing the flow rate properly can be one of the good options that we can use. Hence, it is concluded that a suitable adjustment of the skin-to-core ratio and a proper flow rate control can be used to optimize the core material distribution in multi-cavity co-injection molding with a bifurcation runner structure. Lastly, in order to validate the inference and the effectiveness of this proposal to improve the inter-cavity imbalance and core break-through problem, a series of experimental studies were performed. And, all experimental results are in good agreement with those of our numerical predictions to further validate the feasibility of our proposed method to gain a better control of the core material distribution with a bifurcation runner structure in multi-cavity co-injection molding.