Fluorescence and photoacoustic (PA) imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has garnered massive interest owing to high maximum permissible exposure of light, reduced autofluorescence, and improved deep penetration. However, active targeted NIR-II photoacoustic/NIR-IIa fluorescence imaging of glioma under NIR-II excitation has been seldom reported, which is partly ascribable to the lack of suitable materials. In this study, a small-molecule-based αvβ3-targeted NIR-II photoacoustic/NIR-IIa fluorescent probe IR-32p was generated and subsequently evaluated in U87MG tumor-bearing mice excited with NIR-I and NIR-II light. Exceptional dual-modal imaging properties such as good tumor uptake, high targeting specificity, and high tumor contrast were achieved in an orthotopic glioma model under 1020/1064 nm excitation, exhibiting a superior imaging depth of glioma through the skull. Our study introduces an outstanding dual-modal contrast agent with NIR-II absorption and confirms the superiority of NIR-II excitation over NIR-I in in vivo NIR-II/PA imaging.