Joining of stainless steel and copper is of interest to a variety of applications that range from heat exchanger to nuclear waste container. Nevertheless, welding of these dissimilar metals is challenging because of the risk of hot cracks and lack of fusion associated with their differences in melting temperatures and thermal conductivities. In this work, joining of 316L stainless steel and copper by high velocity oxyfuel is investigated using two systems of materials, the first consisting of copper coatings on AISI 316 substrates, and the second of 316L coatings on copper substrates. To promote metallurgical bonding, the systems were exposed to 500°C, 700°C, 900°C, and 950°C for 10 h under flowing argon atmosphere. Microstructure was characterized by optical and scanning electron microscopy and energy-dispersive x-ray spectroscopy. Bending tests were carried out to qualitatively investigate the coatings adhesion and cohesion strength. It was found that 316L coatings have a much superior adhesion to copper substrates than copper coatings had to AISI 316 substrates, associated with the ease of 316L incoming particles to embed in the softer copper matrix and with the higher susceptibility of 316L coatings to diffuse into copper substrates. In contrast, in copper coatings, copper oxides formed during deposition decomposed during heat treatment, releasing oxygen that caused porosity and oxidation on the interface with the stainless-steel substrate, preventing the formation of a clean metallurgical bond. Diffusion of iron-rich oxide inward the copper coating was also observed near the interface, indicating that diffusion of steel into copper is more likely than diffusion of copper into steel. Nevertheless, heat exposure was found to increase damage tolerance of copper coatings, associated with a higher coating ductility and compliance.