We report the theoretical and experimental investigation of a self-starting mode-locked fiber laser with a nanoengineered Tm3+-doped yttrium-alumina-silica (YAS) fiber as the gain medium. The YAS fiber exhibits a higher capability of Tm3+ cluster elimination than commercial silica fibers. The Tm3+ fluorescence properties and YAS dispersion are well characterized. As a result, an efficient picosecond mode-locked fiber laser is demonstrated with a slope efficiency of 14.14% and maximum pulse energy of 1.27 nJ. To the best of our knowledge, this is the first mode-locked fiber laser based on a Tm3+-doped YAS fiber. The experimental observation is also supported by the numerical analysis.