Integration technologies involving flexible substrates are receiving significant attention owing the appearance of new products regarding wearable and Internet of Things technologies. There has been a continuous demand from the industry for a reliable bonding method applicable to a low-temperature process and flexible substrates. Up to now, however, an anisotropic conductive film (ACF) has been predominantly used in applications involving flexible substrates; we therefore suggest low-temperature lead-free soldering and bonding processes as a possible alternative for flex-on-flex applications. Test vehicles were designed on polyimide flexible substrates (FPCBs) to measure the contact resistances. Solder bumping was carried out using a solder-on-pad process with Solder Bump Maker based on Sn58Bi for low-temperature applications. In addition, thermocompression bonding of FPCBs was successfully demonstrated within the temperature of 150 °C using a newly developed fluxing underfill material with fluxing and curing capabilities at low temperature. The same FPCBs were bonded using commercially available ACFs in order to compare the joint properties with those of a joint formed using solder and an underfill. Both of the interconnections formed with Sn58Bi and ACF were examined through a contact resistance measurement, an 85 °C and 85% reliability test, and an SEM cross-sectional analysis.