Understanding General Least Squares
The Ω matrix is the matrix of the variance of the error term for each observation. Since we do not observe the true error term, we cannot find the true Ω, but we can try to estimate it.

There are different ways of estimating Ω, and there is some debate in econometrics as to which method is the best but the most common method I think would be to take the square of the observed error divided by (1-h) where h is the projection matrix of your matrix X.