One common way to aggregate 100 columns in pandas is to use the apply() function in combination with a lambda function. You can create a lambda function that applies a desired aggregation method, such as sum, mean, min, max, etc., on the 100 columns. Then, you can apply this lambda function along either rows or columns, using the axis parameter in the apply() function. This approach allows for flexibility in choosing the exact aggregation method and axis of aggregation.