Background: Cancer patient survival can be greatly improved by early detection. Cell-free DNA (cfDNA)-based cancer detection using targeted methylation sequencing (TMS) holds great promise. Here, we report the performance of the first cfDNA TMS kit for early cancer detection. Methods: We developed a comprehensive multi-cancer TMS panel, named “Omni1” (900kb) containing ̃3000 cancer specific hypermethylation markers for the detection of the 16 most prevalent solid tumor cancer types in the US. These selected biomarkers all have high signals in cancer, low signals in normal tissue and close to zero background in plasma. The TMS analysis is empowered by Point-n-Seq DNA enrichment and soft bisulfite sequencing technology. Across the different cancer types, the Point-n-Seq Methylation Index (PMI) derived from the Omni1 panel showed over 10 times the difference in the genomic DNA of tumor compared to normal tissues. 8 to 32 early-stage plasma samples from each of the 7 most prevalent cancer types were used for assay testing. cfDNA extracted from each donor was subjected to our Point-n-Seq TMS analysis with the Omni1 panel. The TMS workflow took around five hours, from cfDNA to a sequencing ready library. 6M reads were assigned to each sample resulting in ̃1400X average raw coverage across the target regions. Results: A computational model to calculate the methylation index and the thresholds were established on independent training data sets for each cancer type. For the testing, specificity was set at 89% (CI = 0.81, 0.97, n = 55 self-claimed healthy individuals). The detection rate for stage I (n = 55) and stage II (n = 56) of all 7 cancer types combined is 65% (CI = 0.53,0.78) and 75% (CI = 0.64, 0.86) respectively. Even within this small sample size, it was clear that the detection sensitivity varied among different cancer types, and it increased from stage I to II: colorectal (65%, n = 20; 75%, n = 12), lung (75% n = 8; 92%, n = 12), pancreas (80%, n = 10; 100%, n = 10), ovary (60%, n = 5; 80%, n = 5), breast (40%, n = 7; 100%, n = 3), and prostate cancer (0%, n = 2; 22% n = 9) for stage I and II respectively. A decrease in sensitivity from stage I to II in liver (100%, n = 3; 60%, n = 5) is possibly due to variability from the small sample size. For the cases of CRC, the detection rates obtained from Omni1 are comparable to the stand-alone CRC560 panel (170 kb). Conclusions: In this study we demonstrated that by leveraging an economy-size panel, a robust methylation sequencing kit, and a straightforward analysis methodology, early cancer detection for multiple cancer types can be done with just 1ml plasma. The kit strategy provides an easy-to-use and distributable solution, without the complications of developing a lab-specific test that uses a large methylation panel and a high sequencing cost.