I recently realized that I don't know of any group that is a nontrivial semidirect product of some symmetric group $S_n$ and another group ($S_n$ being the normal subgroup), except when $n=6$. (For instance, $\operatorname{Aut}(S_6) \cong S_6 \rtimes C_2$.) I believe that this is because all outer automorphism groups of $S_n$ are trivial except when $n = 6$.
In fact I believe this stronger statement is true:
If $\phi,\psi:H \to \operatorname{Aut}(K)$ induce the same map $H \to \operatorname{Out}(K)$, then $K \rtimes_\phi H \cong K \rtimes_\psi H$.
Writing things out, the hypothesis means that for all $h \in H$, there exists some $k_0 \in K$ (possibly dependent on $h$) such that $\phi_h(k) = k_0\psi_h(k)k_0^{-1}$ for all $k \in K$. (So this essentially reduces to this unanswered question modulo the fact that $k_0$ varies with $h$.)
If our isomorphism $\theta:K \rtimes_\phi H \to K \rtimes_\psi H$ is to be of the form $\theta(k,h) = (\alpha(k),h)$ for some bijection $\alpha$, then for $\theta$ to be a homomorphism we must have equality between the expressions $$\theta((k,h)(k',h')) = \theta(k\phi_h(k'),hh') = (\alpha(k\phi_h(k')),hh')$$ and $$\theta(k,h)\theta(k',h') = (\alpha(k),h)(\alpha(k'),h') = (\alpha(k)\psi_h(\alpha(k')),hh'),$$
i.e., we must have $$\alpha(k\phi_h(k')) = \alpha(k)\psi_h(\alpha(k')) = \alpha(k)k_0^{-1}\phi_h(\alpha(k'))k_0.$$
I really don't see how we can choose such an $\alpha$. But maybe $\theta$ has a more complicated form. (Or maybe the statement is false!)
Update: As Derek Holt has shown below, the statement is false in this generality. What can we say if $Z(K) = 1$, i.e., $K \cong \operatorname{Inn}(K)$? This is the case for $S_n$ ($n \geq 3$), for instance.