The circuit simulation issue stemmed from multiple incorrect connections, including pin 3 being left hanging and the output directly connected to ground, resulting in a 0V output. The power supply's relation to ground was also problematic, leading to potential op-amp lock-up. After correcting the connections and ensuring the oscilloscope was measuring output voltage against ground, a gain was finally observed. However, the output was initially overdriven due to an input signal that exceeded the op-amp's supply limits. Reducing the input voltage allowed the circuit to function correctly, achieving the desired gain.