diff --git a/packages/grafana-prometheus/src/datasource.test.ts b/packages/grafana-prometheus/src/datasource.test.ts
index dd94b4be299..08104df79b3 100644
--- a/packages/grafana-prometheus/src/datasource.test.ts
+++ b/packages/grafana-prometheus/src/datasource.test.ts
@@ -552,7 +552,7 @@ describe('PrometheusDatasource', () => {
       config.featureToggles.promQLScope = undefined;
     });
 
-    it('should call replace function 2 times', () => {
+    it('should call replace function 3 times', () => {
       const query: PromQuery = {
         expr: 'test{job="testjob"}',
         format: 'time_series',
@@ -563,7 +563,7 @@ describe('PrometheusDatasource', () => {
       replaceMock.mockReturnValue(interval);
 
       const queries = ds.interpolateVariablesInQueries([query], { Interval: { text: interval, value: interval } });
-      expect(templateSrvStub.replace).toBeCalledTimes(2);
+      expect(templateSrvStub.replace).toBeCalledTimes(3);
       expect(queries[0].interval).toBe(interval);
     });
 
@@ -753,6 +753,55 @@ describe('PrometheusDatasource', () => {
       const result = ds.applyTemplateVariables(query, {}, filters);
       expect(result).toMatchObject({ expr: 'test{job="99", k1="v1", k2!="v2"} > 99' });
     });
+
+    it('should replace variables in ad-hoc filters', () => {
+      const searchPattern = /\$A/g;
+      replaceMock.mockImplementation((a: string) => a?.replace(searchPattern, '99') ?? a);
+
+      const query = {
+        expr: 'test',
+        refId: 'A',
+      };
+      const filters = [
+        {
+          key: 'job',
+          operator: '=~',
+          value: '$A',
+        },
+      ];
+
+      const result = ds.applyTemplateVariables(query, {}, filters);
+      expect(result).toMatchObject({ expr: 'test{job=~"99"}' });
+    });
+
+    it('should replace variables in adhoc filters on backend when promQLScope is enabled', () => {
+      config.featureToggles.promQLScope = true;
+      const searchPattern = /\$A/g;
+      replaceMock.mockImplementation((a: string) => a?.replace(searchPattern, '99') ?? a);
+
+      const query = {
+        expr: 'test',
+        refId: 'A',
+      };
+      const filters = [
+        {
+          key: 'job',
+          operator: '=~',
+          value: '$A',
+        },
+      ];
+      const result = ds.applyTemplateVariables(query, {}, filters);
+      expect(result).toMatchObject({
+        expr: 'test',
+        adhocFilters: [
+          {
+            key: 'job',
+            operator: 'regex-match',
+            value: '99',
+          },
+        ],
+      });
+    });
   });
 
   describe('metricFindQuery', () => {
diff --git a/packages/grafana-prometheus/src/datasource.ts b/packages/grafana-prometheus/src/datasource.ts
index ac2e958eccf..34688f47465 100644
--- a/packages/grafana-prometheus/src/datasource.ts
+++ b/packages/grafana-prometheus/src/datasource.ts
@@ -659,14 +659,19 @@ export class PrometheusDatasource
     if (queries && queries.length) {
       expandedQueries = queries.map((query) => {
         const interpolatedQuery = this.templateSrv.replace(query.expr, scopedVars, this.interpolateQueryExpr);
+        const replacedInterpolatedQuery = config.featureToggles.promQLScope
+          ? interpolatedQuery
+          : this.templateSrv.replace(
+              this.enhanceExprWithAdHocFilters(filters, interpolatedQuery),
+              scopedVars,
+              this.interpolateQueryExpr
+            );
 
         const expandedQuery = {
           ...query,
           ...(config.featureToggles.promQLScope ? { adhocFilters: this.generateScopeFilters(filters) } : {}),
           datasource: this.getRef(),
-          expr: config.featureToggles.promQLScope
-            ? interpolatedQuery
-            : this.enhanceExprWithAdHocFilters(filters, interpolatedQuery),
+          expr: replacedInterpolatedQuery,
           interval: this.templateSrv.replace(query.interval, scopedVars),
         };
 
@@ -824,7 +829,11 @@ export class PrometheusDatasource
       return [];
     }
 
-    return filters.map((f) => ({ ...f, operator: scopeFilterOperatorMap[f.operator] }));
+    return filters.map((f) => ({
+      ...f,
+      value: this.templateSrv.replace(f.value, {}, this.interpolateQueryExpr),
+      operator: scopeFilterOperatorMap[f.operator],
+    }));
   }
 
   enhanceExprWithAdHocFilters(filters: AdHocVariableFilter[] | undefined, expr: string) {
@@ -865,12 +874,21 @@ export class PrometheusDatasource
     };
 
     // interpolate expression
+
+    // We need a first replace to evaluate variables before applying adhoc filters
+    // This is required for an expression like `metric > $VAR` where $VAR is a float to which we must not add adhoc filters
     const expr = this.templateSrv.replace(target.expr, variables, this.interpolateQueryExpr);
 
+    // Apply ad-hoc filters
+    // When ad-hoc filters are applied, we replace again the variables in case the ad-hoc filters also reference a variable
+    const exprWithAdhoc = config.featureToggles.promQLScope
+      ? expr
+      : this.templateSrv.replace(this.enhanceExprWithAdHocFilters(filters, expr), variables, this.interpolateQueryExpr);
+
     return {
       ...target,
       ...(config.featureToggles.promQLScope ? { adhocFilters: this.generateScopeFilters(filters) } : {}),
-      expr: config.featureToggles.promQLScope ? expr : this.enhanceExprWithAdHocFilters(filters, expr),
+      expr: exprWithAdhoc,
       interval: this.templateSrv.replace(target.interval, variables),
       legendFormat: this.templateSrv.replace(target.legendFormat, variables),
     };