This study investigates the reliability of low melt alloys (LMAs) containing gallium (Ga), indium (In), bismuth (Bi), and tin (Sn) for the application as Thermal interface materials (TIMs). The analysis described herein involved the in situ thermal performance of the LMAs as well as performance evaluation after accelerated life cycle testing, which included high temperature aging at 130 °C and thermal cycling from −40 °C to 80 °C. Three alloys (75.5Ga & 24.5In, 100Ga, and 51In, 32.5Bi & 16.5Sn) were chosen for testing the thermal performance. Testing methodologies used follow ASTM D5470 protocols and the performance of LMAs is compared with some high-performing commercially available TIMs. Results show that LMAs can offer extremely low (<0.01 cm2 °C/W) thermal resistance compared to any commercial TIMs. The LMA–substrate interactions were explored using different surface treatments (copper and tungsten). Measurements show that depending on the substrate–alloy combinations, the proposed alloys survive 1500 hrs of aging at 130 °C and 1000 cycles from −40 °C to 80 °C without significant performance degradation. The obtained results indicate the LMAs are very efficient as TIMs.