An improved independent component regression (M-ICR) algorithm is proposed by constructing joint latent variable (LV) based regressors, and a quantitative statistical analysis procedure is designed using a bootstrap technique for model validation and performance evaluation. First, the drawbacks of the conventional regression modeling algorithms are analyzed. Then the proposed M-ICR algorithm is formulated for regressor design. It constructs a dual-objective optimization criterion function, simultaneously incorporating quality-relevance and independence into the feature extraction procedure. This ties together the ideas of partial-least squares (PLS), and independent component regression (ICR) under the same mathematical umbrella. By adjusting the controllable suboptimization objective weights, it adds insight into the different roles of quality-relevant and independent characteristics in calibration modeling, and, thus, provides possibilities to combine the advantages of PLS and ICR. Furthermore, a quantitative statistical analysis procedure based on a bootstrapping technique is designed to identify the effects of LVs, determine a better model rank and overcome ill-conditioning caused by model over-parameterization. A confidence interval on quality prediction is also approximated. The performance of the proposed method is demonstrated using both numerical and real world data.