Édouard Vuillard (1868–1949) is well known for his small atmospheric paintings, often portraying his own home and family as the subject matter. Interior, Mother and Sister of the Artist (1893) underwent at least one restoration treatment before being acquired by the Museum of Modern Art (MoMA) in 1934. The painting was treated again in 1954, but no analysis was carried out to understand the artist’s methods and materials at that time. To better understand the choices of Vuillard in Interior, Mother and Sister of the Artist, a comprehensive suite of imaging and spectroscopic analyses was undertaken, including: XRR, UVF and IRR Photography, XRF, Raman spectroscopy and SERS, and µ-FTIR. Statistical analysis on the XRF data using MCR-ALS further revealed some of the intricacies of Vuillard’s technique and color choices, where a large number of pigments were used in designing this intimate composition, including lead white, zinc white, bone black, ochre, umber, vermilion, Geranium lake, red lead, ultramarine, Prussian blue, chrome yellow, chrome orange, zinc yellow, strontium yellow, cadmium yellow, and a chromium oxide green.