We comparatively studied the wetting behavior of water droplets on graphene and biphenylene using molecular dynamics simulations. The research showed that pristine biphenylene (BPN), unlike graphene, exhibits greater hydrophobicity and anisotropic wettability. This specific anisotropy can be tuned by the layer number and vacancy concentration. Particularly, there was a decrease in the water contact angle with increasing BPN layer number, highlighting the importance of water-BPN interactions. As the concentration of vacancies increases, the contact angle increases both along the zigzag direction and the armchair direction, while the anisotropy decreases. In planar defective biphenylene heterojunctions, water droplets spontaneously move from the defective area to the pristine area, where the zigzag direction exhibits a larger energy gradient compared to the armchair direction, leading to a faster movement of water droplets in the zigzag direction. The energy factor plays an important role in the directional movement of the water droplets. Our study explores new 2D materials with strong hydrophobicity and highlights the direction-dependent wetting behavior of biphenylene.