This study investigates the wettability and confinement size effects on vibration and stability of water conveying nanotubes. We present an accurate assessment of nanotube stability by considering the exact mechanics of the fluid that is confined in the nanotube. Information on the stability of nanotubes in relation to the fluid viscosity, the driving force of the fluid flow, the surface wettability of the nanotube, and the nanotube size is missing in the literature. For the first time, we explore the surface wettability dependence of the nanotube natural frequencies and stability. By means of hybrid continuum-molecular mechanics (HCMM), we determined water viscosity variations inside the nanotube. Nanotubes with different surface wettability varying from super-hydrophobic to super-hydrophilic nanotubes were studied. We demonstrated a multiphase structure of nanoconfined water in nanotubes. Water was seen as vapor at the interface with the nanotube, ice shell in the middle, and liquid water in the nanotube core. The average velocity of water flow in the nanotube was obtained strongly depend on the surface wettability and the confinement size. In addition, we report the natural frequencies of the nanotube as functions of the applied pressure and the nanotube size. Mode divergence and flutter instabilities were observed, and the activation of these instabilities strongly depended on the nanotube surface wettability and size. This work gives important insights into understanding the stability of nanotubes conveying fluids depending on the operating pressures and the wettability and size of confinement. We revealed that hydrophilic nanotubes are generally more stable than hydrophobic nanotubes when conveying fluids.