Due to the complex nature of a variable cycle engine (VCE), which has numerous control variables and working modes across a broad flight envelope, coupled with the whole engine’s degradation, the analytical redundancy method based on component-level models may not provide an accurate estimation of the sensors. Variable-weights-biases neural network (VWB Net) is proposed to construct VCE’s analytical redundancy. Unlike conventional networks whose weights and biases are fixed, VWB Net’s variable-weights and variable-biases are functions of input which greatly increase its nonlinear mapping capability by integrating input information. Variable-biases can also be used to eliminate the error between actual sensor output and estimated value quickly at the terminal node. Compared with the BP network and Dense net, VWB Net has fewer parameters, faster calculation speed, and higher accuracy. Digital simulation results of VCE parameter estimation demonstrate that VWB Net’s average relative errors are under 0.27% with calculation and parameter efficiency at least 166 times higher than that of Dense net. Hardware in the loop simulation further verifies VWB Net’s estimation accuracy and real-time calculation.