Multimodality imaging-guided therapy based on lanthanide-doped upconversion nanoparticles (UCNPs) has become a trend in cancer theranostics. However, the overheating effect of 980 nm excitation in photodynamic therapy (PDT) and the difficulties in optimizing multimodality imaging integration within a single particle are still challenges. Herein, 800 nm driven NaErF4@NaLuF4 UCNPs have been explored for optimized multimodality imaging and near-infrared (NIR) triggered PDT. Our results confirmed that the optimal ∼5 nm shell thickness can well balance the enhancement of upconversion luminescence and the attenuation of energy transfer efficiency from Er3+ towards a photosensitizer, to achieve efficient production of singlet oxygen (1O2) for PDT under 800 nm excitation. Furthermore, the as-obtained NaErF4@NaLuF4 UCNPs showed effective and applicable performance for upconversion luminescence (UCL) imaging, X-ray computed tomography (CT), and high-field T2 magnetic resonance imaging (MRI). This nanomaterial can serve as an excellent theranostic agent for multimodality imaging and image-guided therapy.