Anisotropic hyperbolic phonon polaritons (PhPs) in natural biaxial hyperbolic material α-MoO3 has opened up new avenues for mid-infrared nanophotonics, while active tunability of α-MoO3 PhPs is still an urgent problem needing to be solved. In this study, we present a theoretical demonstration of actively tuning α-MoO3 PhPs using phase change material VO2 and graphene. It is observed that α-MoO3 PhPs are greatly dependent on the propagation plane angle of PhPs. The insulator-to-metal phase transition of VO2 has a significant effect on the hybridization PhPs of the α-MoO3/VO2 structure and allows to obtain an actively tunable α-MoO3 PhPs, which is especially obvious when the propagation plane angle of PhPs is 90°. Moreover, when graphene surface plasmon sources are placed at the top or bottom of α-MoO3 in α-MoO3/VO2 structure, tunable coupled hyperbolic plasmon–phonon polaritons inside its Reststrahlen bands (RBs) and surface plasmon–phonon polaritons outside its RBs can be achieved. In addition, the above-mentioned α-MoO3-based structures also lead to actively tunable anisotropic spontaneous emission (SE) enhancement. This study may be beneficial for the realization of active tunability of both PhPs and SE of α-MoO3, and facilitate a deeper understanding of the mechanisms of anisotropic light-matter interaction in α-MoO3 using functional materials.