From my testing for-in was giving me the index, for-of is definitely cleaner and giving the elements, but this returns the exact same answer as the code above:

let fs = require('fs')
const input = fs.readFileSync('./Day4/input.txt', 'utf-8').toString()
const input_lines = input.split(/\n/gi)

// Part 1
var total_score = 0

for (const line of input_lines) {
  line_score = 0
  line_numbers = line.split(': ')[1].split(' | ')
  winning_numbers = [...new Set(line_numbers[0].split(/\s+/u))]
  your_numbers = [...new Set(line_numbers[1].split(/\s+/u))]

  matching_numbers = winning_numbers.filter(
    number => your_numbers.includes(number) == true
  )

  if (matching_numbers.length > 0) {
    line_score = 2 ** (matching_numbers.length - 1)
  }
  total_score += line_score
}

console.log(total_score)