It is possible to do it: the only thing to remember is that the tikzpicture should be vertically aligned with the rest of the formula. To achieve this result you can use the option [baseline=-0.5ex].
Here is a MWE:
\documentclass{article}
\usepackage{amsmath,amssymb}
\usepackage{tikz}
\usetikzlibrary{matrix,calc}
\begin{document}
\begin{align*}
P&=
\begin{tikzpicture}[baseline=-0.5ex]
\matrix[matrix of math nodes,left delimiter=(,right delimiter=),inner sep=2.5pt, column 2/.style={green!50!black},
ampersand replacement=\&] % <= to change col separator for align env
{
x_1 \& y_1 \\
x_2 \& y_2 \\
x_3 \& y_3 \\
x_4 \& y_4 \\
};
\end{tikzpicture}
+
\begin{pmatrix}
z_1 & w_1 \\
z_2 & w_2 \\
z_3 & w_3 \\
z_4 & w_4 \\
\end{pmatrix}
\end{align*}
\end{document}
that gives you:

EDIT
Thanks to egreg's comment, I edit the answer to show with a picture the differences between the settings:
baseline=-0.5ex
baseline=-\the\dimexpr\fontdimen22\textfont2\relax
Code:
\documentclass{article}
\usepackage{amsmath,amssymb}
\usepackage{tikz}
\usetikzlibrary{matrix,calc}
\begin{document}
\begin{tikzpicture}[baseline=-0.5]
%\let\&=\pgfmatrixnextcell % <= one choice to change col separator
\matrix[matrix of math nodes,left delimiter=(,right delimiter=),inner sep=2.5pt, column 2/.style={green!50!black},
ampersand replacement=\&] % <= to change col separator for align env
{
x_1 \& y_1 \\
x_2 \& y_2 \\
x_3 \& y_3 \\
x_4 \& y_4 \\
};
\end{tikzpicture}
% new setting by egreg
\begin{tikzpicture}[baseline=-\the\dimexpr\fontdimen22\textfont2\relax ]
\matrix[matrix of math nodes,left delimiter=(,right delimiter=),inner sep=2.5pt, column 2/.style={green!50!black},
ampersand replacement=\&] % <= to change col separator for align env
{
x_1 \& y_1 \\
x_2 \& y_2 \\
x_3 \& y_3 \\
x_4 \& y_4 \\
};
\end{tikzpicture}
+$\begin{pmatrix}
z_1 & w_1 \\
z_2 & w_2 \\
z_3 & w_3 \\
z_4 & w_4 \\
\end{pmatrix}
$
\end{document}
In the following picture the first matrix still have the option baseline=-0.5 and it is a bit lower the other two matrices.
