Advancements in high–throughput microscopy imaging have transformed cell analytics, enabling functionally relevant, rapid, and in–depth bioanalytics with Artificial Intelligence (AI) as a powerful driving force in cell therapy (CT) manufacturing. High–content microscopy screening often suffers from systematic noise, such as uneven illumination or vignetting artifacts, which can result in false–negative findings in AI models. Traditionally, AI models have been expected to learn to deal with these artifacts, but success in an inductive framework depends on sufficient training examples. To address this challenge, we propose a two–fold approach: (1) reducing noise through an image decomposition and restoration technique called the Periodic Plus Smooth Wavelet transform (PPSW) and (2) developing an interpretable machine learning (ML) platform using tree–based Shapley Additive exPlanations (SHAP) to enhance end–user understanding. By correcting artifacts during pre–processing, we lower the inductive learning load on the AI and improve end–user acceptance through a more interpretable heuristic approach to problem solving. Using a dataset of human Mesenchymal Stem Cells (MSCs) cultured under diverse density and media environment conditions, we demonstrate supervised clustering with mean SHAP values, derived from the ‘DFT Modulus’ applied to the decomposition of bright–field images, in the trained tree–based ML model. Our innovative ML framework offers end-to-end interpretability, leading to improved precision in cell characterization during CT manufacturing.