Gene fusions are one of the most important molecular biomarkers for tumor diagnosis, classification and targeted therapy. How to accurately detect them is a key issue in clinical work. In this study, a custom-designed integration of DNA and RNA-based next generation sequencing (NGS) assay including 16 targeted therapy related genes was developed and validated to identify gene fusions in solid tumors. This assay accurately identified all 10 different types of fusion in 8 commercial fusion spiked-in reference standards and 29 fusions including 16 different fusion forms in 60 clinical solid tumor samples previously identified by clinical testing methods. In addition, a TPM3::NTRK1 fusion was additionally identified and validated by Sanger sequencing, which showed a false-negative result for the previous result. Mutational abundance limit of detection for the assay was assessed with a series of dilution experiments. These fusions can be stably detected when the mutational abundance is down to 5% for DNA and 250-400 copies/100 ng for RNA. The intra-assay and inter-assay reproducibility was observed in three samples and three replicates. This integration of DNA and RNA-based NGS assay shows excellent performance on formalin-fixed, paraffin-embedded samples, results at different levels can complement each other, thereby facilitating precise diagnosis and treatment.