Domenico Piola was taught to paint by his brother, Pellegro Piola (1617-1640). He later worked in partnership with his younger brother, Giovanni Andrea Piola (1627-c. 1713); his three sons Paolo Gerolamo Piola (1666-1724), Anton Maria Piola (1654-1715) and Giovanni Battista Piola (d. 1725); his two sons-in-law, Gregorio de' Ferrari and Domenico Parodi (1668-1740)); and his brother-in-law Stefano Camogli (active 1665-1690), a specialist in arabesques of flowers and fruit. From the time of Luca Cambiaso, Genoese ceilings had consisted of rich decorative frescoes surrounded by elaborate ornament.
From the latter half of the 17th century and into the early 18th century the Casa Piola came to dominate and unify the production of the various elements involved: quadratura, stucco, sculpture and painting. The workshop's eminence in all these media enabled it to achieve an artistic monopoly that partially accounts for the decorative consistency in Genoa in the last half of the century. Large decorative projects were comprehensively prepared through drawings, progressing from careful studies of details through compositional sketches to full-scale cartoons. In their decorative projects featuring illusionistic effects the Casa Piola also designed the quadratura, which, to judge from drawings, was often as important to them as the central section of the vault. They also regarded sculpture as an integral part of the design and supplied designs for sculptors, among them Filippo Parodi, Antonio Maria Maragliano (1664-1739), Bernardo Schiaffino (1680-1725) and Francesco Maria Schiaffino.
Drawings for altars, tabernacles, ship ornaments, clocks, ceramics and metalwork indicate that the workshop also supplied ideas for craftsmen to elaborate. Paolo Gerolamo succeeded his father as head of the workshop and the studio ended with the death of Giovanni Battista Piola, Piola's great grandson, in 1768.