The first question that should be asked of any person presenting you with a large-ish matrix: "is the matrix dense or sparse?" In the latter case, one definitely does not need to allocate space for the zero entries, and should thus look into special techniques to storing them(which as I understand nowadays rely on a liberal dose of graph theory in the general case, though band matrices are still handled by storing their bands in an appropriate format).
Now, if even after that you have the perfect excuse for having a large dense matrix (which I still believe is quite unlikely), there is a way to invert and take the determinant of a large matrix via partitioning.
Say we have
$\textbf{A}=\begin{pmatrix}\textbf{E}&\textbf{F}\\ \textbf{G}&\textbf{H}\end{pmatrix}$
where $\textbf{E}$ and $\textbf{H}$ are square matrices with dimensions $m\times m$ and $n\times n$ respectively, and $\textbf{F}$ and $\textbf{G}$ are dimensioned appropriately (so the dimension of $\textbf{A}$ is $(m+n)\times(m+n)$). The inverse can then be computed as
$\textbf{A}^{-1}=\begin{pmatrix}\textbf{E}^{-1}+\left(\textbf{E}^{-1}\textbf{F}\right)(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\right)&-\left(\textbf{E}^{-1}\textbf{F}\right)(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\\-(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\right)&(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\end{pmatrix}$
where the parentheses emphasize common factors that you might profit from computing only once.
As for the determinant, it is given by
$\det\;\textbf{A}=\det\left(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F}\right)\;\det\;\textbf{E}$
EDIT:
I'm not entirely sure what seemed to be unsatisfactory with this answer, so here's a bit more of exposition: as always, the "inverse" here is merely notation! One would most certainly first perform LU decomposition on $\textbf{E}$ and $\textbf{H}$ first. One would also partition the right-hand side $\textbf{b}$ accordingly:
$\textbf{b}=\begin{pmatrix}\textbf{c}\\ \textbf{d}\end{pmatrix}$
so $\textbf{c}$ is a length-m vector and $\textbf{d}$ is a length-n vector.
Formally multiplying the partitioned inverse with the partitioned right-hand side gives
$\begin{pmatrix}\textbf{E}^{-1}+\left(\textbf{E}^{-1}\textbf{F}\right)(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\right)&-\left(\textbf{E}^{-1}\textbf{F}\right)(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\\-(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\right)&(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\end{pmatrix}\cdot\begin{pmatrix}\textbf{c}\\ \textbf{d}\end{pmatrix}$
which when expanded and simplified is
$\begin{pmatrix}\textbf{E}^{-1}\textbf{c}+\left(\textbf{E}^{-1}\textbf{F}\right)(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\textbf{c}-\textbf{d}\right)\\-(\textbf{H}-\textbf{G}\textbf{E}^{-1}\textbf{F})^{-1}\left(\textbf{G}\textbf{E}^{-1}\textbf{c}-\textbf{d}\right)\end{pmatrix}$
At this point you should be able to figure out how you would use an available decomposition of $\textbf{E}$ or $\textbf{H}$, and which common subexpressions can be just computed once.