Region of interest (ROI) extraction is a fundamental step in analyzing metabolomic datasets acquired by liquid chromatography-mass spectrometry (LC-MS). However, noises and backgrounds in LC-MS data often affect the quality of extracted ROIs. Therefore, developing effective ROI evaluation algorithms is necessary to eliminate false positives meanwhile keep the false-negative rate as low as possible. In this study, a deep fused filter of ROIs (dffROI) was proposed to improve the accuracy of ROI extraction by combining the handcrafted evaluation metrics with convolutional neural network (CNN)-learned representations. To evaluate the performance of dffROI, dffROI was compared with peakonly (CNN-learned representation) and five handcrafted metrics on three LC-MS datasets and a gas chromatography-mass spectrometry (GC-MS) dataset. Results show that dffROI can achieve higher accuracy, better true-positive rate, and lower false-positive rate. Its accuracy, true-positive rate, and false-positive rate are 0.9841, 0.9869, and 0.0186 on the test set, respectively. The classification error rate of dffROI (1.59%) is significantly reduced compared with peakonly (2.73%). The model-agnostic feature importance demonstrates the necessity of fusing handcrafted evaluation metrics with the convolutional neural network representations. dffROI is an automatic, robust, and universal method for ROI filtering by virtue of information fusion and end-to-end learning. It is implemented in Python programming language and open-sourced at https://github.com/zhanghailiangcsu/dffROI under BSD License. Furthermore, it has been integrated into the KPIC2 framework previously proposed by our group to facilitate real metabolomic LC-MS dataset analysis.