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It marks 週末 as the thing being looked forward to in the set phrase X を楽しみにする. Think: “to have X as something to look forward to.” You cannot replace it with に here, because に already appears as part of 楽しみに (see below).

Why is 彼女 followed by は and not が?

は marks the topic: “As for her, …” It’s natural when she is already known in the conversation.
が would answer a “who?” question or introduce her as new/contrastive information: “It’s she who is looking forward to the weekend.” Both are possible depending on context; は is the neutral topic choice here.

Why is the noun 楽しみ used instead of the verb 楽しむ?

楽しみ is a noun meaning “pleasure” or “something to look forward to.” With にする, it makes the idiom 楽しみにする = “to look forward to.”
楽しむ is a verb meaning “to enjoy (while doing/experiencing).” For example, 週末を楽しむ = “enjoy the weekend (when it arrives).” So 楽しみにしている is about anticipation, not about enjoying in the moment.

What does に in 楽しみに mean here?

It’s the に from the pattern N にする (“to make/put something into state N”). In the idiom X を楽しみにする, you’re putting X into the category of “things I’m looking forward to.” Treat 楽しみにする as a fixed expression; that に is required.

What does している add to the meaning?

〜ている indicates a continuing state. 楽しみにしている means “is in the state of looking forward to (right now / these days),” not just a one-off act of deciding to look forward to something. It’s the natural way to describe a current, ongoing feeling.

How do I say this more politely?

Use 彼女は週末を楽しみにしています。 That’s standard polite. An extra-formal version is 楽しみにしております, but that humble style is normally used for yourself/your in-group in business contexts, not for a third person like 彼女.

What’s the difference between 週末を楽しみにしている and 週末が楽しみだ?

Both mean “(She) is looking forward to the weekend.”

週末が楽しみだ: shorter, more stative description (“The weekend is a source of joy”).
週末を楽しみにしている: emphasizes the ongoing act/feeling of anticipation. Polite versions: 週末が楽しみです / 週末を楽しみにしています.

Can I say 週末を楽しんでいる instead?

That means “She is enjoying the weekend (now).” Use it when the weekend is happening and she’s actively enjoying it. It does not mean “looking forward to.”

Can I omit 彼女?

Yes. Japanese often drops subjects when they’re clear from context. You can just say 週末を楽しみにしている. Be aware it then becomes ambiguous (I/you/he/she), and the listener infers who from context.

Can I make 週末 the topic: 週末は楽しみにしている? What changes?

It’s possible and suggests contrast or generality:

Contrast: “As for the weekend (as opposed to weekdays), she looks forward to it.”
General/habitual: could sound like “Weekends (in general) are something she looks forward to.” If you mean the next/this weekend specifically, say 今度の週末は楽しみにしている or この週末は….

Why are there spaces between the words?

They’re for learner readability. Standard Japanese is written without spaces: 彼女は週末を楽しみにしている。

How do I change the tense or make it negative?

Past: 楽しみにしていた (was looking forward to)
Negative: 楽しみにしていない (is not looking forward to)
Past negative: 楽しみにしていなかった Polite versions: しています／していません／していました. To be specific about time, add words like 来週末 or 今度の週末.

How can I strengthen or soften the feeling?

Stronger: とても／すごく／本当に → 彼女は週末を本当に楽しみにしている。
Very casual strong: めっちゃ (informal) → めっちゃ楽しみにしてる。
Softer: 少し／ちょっと → 少し楽しみにしている。
Duration/emphasis: ずっと → ずっと週末を楽しみにしている。

Are there natural synonyms or alternatives?

週末が待ち遠しい。 (She can’t wait for the weekend.)
週末を心待ちにしている。 (Somewhat literary/formal.)
週末が楽しみだ。 (Concise alternative.) Avoid 期待している here; it’s “to expect,” which can sound different from “looking forward to.”

Why not say 楽しみをしている?

Because the idiom is 楽しみにする, not 楽しみをする. N をする means “to do N,” but 楽しみ (“a pleasure”) isn’t something you “do.” The に is essential in this expression.

Is the contraction してる okay?

Yes, in casual speech/writing: 楽しみにしてる. Use している／しています in formal or written contexts.