The rapid development of spatial transcriptomics (ST) allows researchers to measure the spatial-level gene expression in tissues. Although powerful, the cost for collecting the ST data is expensive, and thus several studies aim to predict gene expression in ST by utilizing their corresponding H/E stained pathology images. The existing ST based gene expression prediction models either adopt the pre-trained networks or rely on the handcrafted features to describe the pathology images, which still lack a systematic way to combine them together to define a spot-level representation that can reflect the topological profiles of different spots. On the other hand, all the ST based gene prediction models treat the prediction task for each gene independently, which overlook the fact that the exploration of potential interrelationships among them can help improve the prediction performance for individual genes.To address the above issues, we propose a multi-modal topology-embedded graph learning algorithm guided by prior Gene Ontology similarity information (i.e., M2TGLGO) to predict the spatial resolved genes from pathology image. Specifically, M2TGLGO co-learns the image representation of different spots from both deep and handcrafted features by considering the within-modal and inter-modal interactions. Next, to keep the topological structure among different spots, a spatial-oriented ranking module is also incorporated to preserve their neighborhood similarity information. Finally, we present a Gene Ontology knowledge guided graph neural network for simultaneously predicting multiple gene expressions by considering their functional associations. We evaluate our method on three public available ST datasets, the experimental results show the effectiveness of our M2TGLGO in comparison with the existing studies.